Combination of a CB1 receptor antagonist and of sibutramine, the pharmaceutical compositions comprising them and their use in the treatment of obesity

ABSTRACT

The present invention relates to the combination of a CB1 receptor antagonist and of sibutramine, to the pharmaceutical compositions comprising them and to their use in the treatment of obesity.

[0001] The present invention relates to the combination of a CB1receptor antagonist and of sibutramine, to the pharmaceuticalcompositions comprising them and to their use in the treatment ofobesity.

[0002] CB1 receptor antagonists are known for their effect on foodintake and their use as anorexigenic (G. Colombo et al., Life Sciences,63 (8), 113-117 (1998); J. Siamand et al., Behavioural Pharmacol., 9,179-181 (1998)).

[0003] Sibutramine (BTS 54524;N-{1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutyl}-N,N-dimethylamine;Meridia^(R), Reductil^(R)), its hydrate and its pharmaceuticallyacceptable salts and in particular its hydrochloride reduces food intakeand is of use in the treatment of obesity (WO 90/061110; D. H. Ryan etal., Obesity Research, 3 (4), 553 (1995); H. C. Jackson et al., BritishJournal of Pharmacology, 121, 1758 (1997); G. Fanghanel et al., Inter.J. Obes., 24 (2), 144 (2000); G. A. Bray et al., Obes. Res., 7 (2), 189(1999)).

[0004] It has now been found that the combination of sibutramine, itshydrate and its pharmaceutically acceptable salts and of a CB1 receptorantagonist exhibits a synergistic effect in reducing food consumptionand is thus of use in the treatment of obesity.

[0005] The combination can also comprise several CB1 receptorantagonists.

[0006] Use may in particular be made, among CB1 [lacuna] antagonists, ofthe azetidine derivatives disclosed in WO 00/15609, WO 01/64633 and WO01/64634 of formula:

[0007] in which

[0008] either R represents a chain (A) or (B) and

[0009] R₁represents a methyl or ethyl radical,

[0010] R₂ represents either ani aromatic chosen from phenyl, naphthyl orindenyl, these aromatics being unsubstituted or substituted by one ormore halogen, alkyl, alkoxy, —CO-alk, hydroxyl, —COOR₅, formyl,trifluoromethyl, trifluoromethylsultanyl, trifluoromethoxy, nitro,—NR₆R₇, —CO—NH—N₆R₇, —N(alk)COOR_(B), cyano, —CONHR₉, —CO—NR₁₆R₁₇,alkylsulfanyl, hydroxyalkyl, —O-alkNR₁₂R₁₃ or alkylthioalkyl, or aheteroaromatic chosen from the benzofuryl, benzothiazolyl, benzothienyl,benzoxazolyl, chromanyl, 2,3-dihydrobenzofuryl, 2,3-dihydrobenzothienyl,indolinyl, indolyl, isochromanyl, isoquinolyl, pyridyl, quinolyl,1,2,3,4-tetrahydroisoquinolyl, 1,2,3,4-tetrahydroquinolyl, thiazolyl orthienyl rings, it being possible for these heteroaromatics to beunsubstituted or substituted by a halogen, alkyl, alkoxy, —COOR₅,trifluoromethyl, trifluoromethylsulfanyl, trifluoromethoxy, nitro,—NR₆R₇, —CO—NH—NR₆R₇, cyano, —CONHR₉, alkylsulfanyl, hydroxyalkyl oralkylthioalkyl,

[0011] R₃ and R₄, which are identical or different, represent either anaromatic chosen from phenyl, naphthyl or indenyl, these aromatics beingunsubstituted or substituted by one or more halogen, alkyl, alkoxy,formyl, hydroxyl, trifluoromethyl, trifluoromethoxy, —CO-alk, cyano,—COOR₅, —CONR₁₀R₁₁, —CO—NH—NR₆R₇, alkylsulfanyl, hydroxyalkyl,-alk-NR₆R₇ or alkylthioalkyl, or a heteroaromatic chosen from thebenzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, chromanyl,2,3-dihydrobenzofuryl, 2,3-dihydrobenzothienyl, furyl, isochromanyl,isoquinolyl, pyrrolyl, quinolyl, 1,2,3,4-tetrahydroisoquinolyl,thiazolyl or thienyl rings, it being possible for these heteroaromaticsto be unsubstituted or substituted by a halogen, alkyl, alkoxy,hydroxyl, trifluoromethyl, trifluoromethoxy, cyano, —COOR₅,—CO—NH—NR₆R₇, -CONR₁₀R₁₁, -alk-NR₆R₇, alkylsulfanyl, hydroxyalkyl oralkylthioalkyl,

[0012] R₅ is an alkyl radical or a phenyl radical optionally substitutedby one or more halogen atoms,

[0013] R₆ and R₇, which are identical or different, represent a hydrogenatom or an alkyl, -COOalk, cycloalkyl, alkylcycloalkyl, -alk-O-alk orhydroxyalkyl radical or else R₆ and R₇ form, together with the nitrogenatom to which they are attached, a saturated or unsaturated and mono- orbicyclic heterocycle having 3 to 10 ring members optionally comprisinganother heteroatom chosen from oxygen, sulfur and nitrogen andoptionally being substituted by one or more alkyl, -COalk, -COOalk,—CO-NHalk, —CS-NHalk, —CO-alk-NR₁₄R₁₅, oxo, hydroxyalkyl, -alk-O-alk or—CO—NH₂ radicals,

[0014] R₈ represents an alkyl radical,

[0015] R₉ represents a hydrogen atom or a radical of the type alkyl oralkyl substituted by dialkylamino, phenyl, cycloalkyl (optionallysubstituted by -COOalk) or a saturated or unsaturated and mono- orbicyclic heterocycle having 3 to 10 ring members optionally comprisingone or more heteroatoms chosen from oxygen, sulfur and nitrogen andoptionally being substituted by one or more alkyl radicals,

[0016] R₁₀ and R₁₁, which are identical or different, represent ahydrogen atom or an alkyl radical or else R₁₀ and R₁₁ form, togetherwith the nitrogen atom to which they are attached, a saturated mono- orbicyclic heterocycle having 3 to 10 ring members optionally comprisinganother heteroatom chosen from oxygen, sulfur and nitrogen andoptionally being substituted by an alkyl radical,

[0017] R₁₂ and R₁₃, which are identical or different, represent ahydrogen atom or an alkyl or cycloalkyl radical or else R₁₂ and R₁₃form, together with the nitrogen atom to which they are attached, asaturated mono- or bicyclic heterocycle having 3 to 10 ring membersoptionally comprising another heteroatom chosen from oxygen, sulfur andnitrogen and optionally being substituted by an alkyl, -COalk, -COOalk,—CO-NHalk, —CS-NHalk or —CO-alk-NR₁₄R₁₅ radical or a saturated mono- orbicyclic heterocycle having 3 to 10 ring members and comprising aheteroatom chosen from oxygen, sulfur and nitrogen,

[0018] R₁₄ and R₁₅, which are identical or different, represent ahydrogen atom or an alkyl or -COOalk radical,

[0019] R₁₆ and R₁₇ form, together with the nitrogen atom to which theyare attached, a saturated mono or bicyclic heterocycle having 3 to 10ring members optionally comprising another heteroatom chosen fromoxygen, sulfur and nitrogen,

[0020] R′ represents a hydrogen atom or a -CO-alk radical,

[0021] or R represents a CHR₁₈ radical and

[0022] R₁₈ represents an —NHCOR₁₉ or —N(R₂₀)—Y—R₂a radical,

[0023] Y is CO or SO₂,

[0024] R₄ and R₃, which are identical or different, represent either anaromatic chosen from phenyl, naphthyl and indenyl, these aromatics beingunsubstituted or substituted by one or more halogen, alkyl, alkoxy,formyl, hydroxyl, trifluoromethyl, trifluoromethoxy, —CO-alk, cyano,—COOH, -COOalk, —CONR₂₂R₂₃, —CO—NH—NR₂₄R₂₅, alkylsulfanyl,alkylsulfinyl, alkylsulfonyl, alkylsulfanylalkyl, alkylsulfinylalkyl,alkylsulfonylalkyl, hydroxyalkyl or -alk-NH₂₂R₂₃, or a heteroaromaticchosen from the benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl,chromanyl, 2, 3-dihydrobenzofuryl, 2,3-dihydrobenzothienyl, pyrimidinyl,furyl, imidazolyl, isochromanyl, isoquinolyl, pyrrolyl, pyridyl,quinolyl, 1,2,3,4-tetrahydroisoquinolyl, thiazolyl and thienyl rings, itbeing possible for these heteroaromatics to be unsubstituted orsubstituted by a halogen, alkyl, alkoxy, hydroxyl, trifluoromethyl,trifluoromethoxy, cyano, —COOH, -COOalk, —CO—NH—NR₂₄R₂₅, —CONR₂₂R₂₃,-alk-NR₂₄R₂₅E, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl,alkylsulfanylalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl orhydroxyalkyl,

[0025] R₁₉ represents an -alk-SO₂-R₂₆ radical, an -alk-SO₂—CH═CH—R₂₆radical, a Het₁ radical substituted by —SO₂—R₂₆ or a phenyl radicalsubstituted by —SO₂—R₂₆ or alk-SO₂—R₂₆,

[0026] R₂₀ represents a hydrogen atom or an alkyl radical,

[0027] R₂₁ represents a phenylalkyl, Het₁ or Ar₁ radical,

[0028] R₂₂ and R₂₃, which are identical or different, represent ahydrogen atom or an alkyl radical or else R₂₂ and R₂₃ form, togetherwith the nitrogen atom to which they are attached, a saturated mono- orbicyclic heterocycle having 3 to 10 ring members optionally comprisinganother heteroatom chosen from oxygen, sulfur and nitrogen andoptionally being substituted by one or more alkyl,

[0029] R₂₄ and R₂₅, which are identical or different, represent ahydrogen atom or an alkyl, -COOalk, cycloalkyl, alkylcycloalkyl,-alk-O-alk or hydroxyalkyl radical or else R₂₄ and R₂₅ form, togetherwith the nitrogen atom to which they are attached, a saturated orunsaturated mono- or bicyclic heterocycle having 3 to 10 ring membersoptionally comprising another heteroatom chosen from oxygen, sulfur andnitrogen and optionally being substituted by one or more alkyl, -COalk,COOalk, —CO-NHalk, —CS-NHalk, oxo, hydroxyalkyl, -alk-O-alk or —CO—NH₂,

[0030] R₂₆ represents an alkyl, Ar₁ or Het₁ radical,

[0031] Ar₁ represents a phenyl, naphthyl or indenyl radical, theseradicals optionally being substituted by one or more halogen, alkyl,alkoxy, cyano, —CO-alk, —COOH, -COOalk, —CONR₂₇R₂₈, CO—NH—NR₂₉R₃₀,alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, -alk-NR₂₉R₃₀, —NR₂₉R₃₀,alkylthioalkyl, formyl, hydroxyl, hydroxyalkyl, Het,0-alk-NH-cycloalkyl, OCF₃, CF₃, —NH—CO-alk, —SO₂NH₂, —NH—COCH₃,—NH—COOalk or Het or else on 2 adjacent carbon atoms by dioxymethylene,

[0032] Het₁ represents an unsaturated or saturated mono- or bicyclicheterocycle having 3 to 10 ring members and comprising one or moreheteroatoms chosen from oxygen, sulfur and nitrogen which is optionallysubstituted by one or more alkyl, alkoxy, vinyl, halogen,alkoxycarbonyl, oxo, hydroxyl, OCF₃ or CF₃, the nitrogenous heterocyclesoptionally being in their N-oxidized form,

[0033] R₂₇ and R₂₈, which are identical or different, represent ahydrogen atom or an alkyl radical or else R₂₇ and R₂₈ form, togetherwith the nitrogen atom to which they are attached, a saturated mono- orbicyclic heterocycle having 3 to 10 ring members optionally comprisinganother heteroatom chosen from oxygen, sulfur and nitrogen andoptionally being substituted by one or more alkyl radicals,

[0034] R₂₉ and R₃₀, which are identical or different, represent ahydrogen atom or an alkyl, -COOalk, cycloalkyl, alkylcycloalkyl,-alk-O-alk or hydroxyalkyl radical or else R₂₉ and R₃₀ form, togetherwith the nitrogen atom to which they are attached, a saturated orunsaturated mono- or bicyclic heterocycle having 3 to 10 ring membersoptionally comprising another heteroatom chosen from oxygen, sulfur andnitrogen and optionally being substituted by one or more alkyl, -COalk,-COOalk, —CO-NHalk, —CS-NHalk, oxo, hydroxyalkyl, -alk-O-alk or —CO—NH₂radicals,

[0035] or R represents CHR₃₁ and

[0036] R₃₁ represents an —N(R₃₂)R₃₃, —N(R₃₂)—CO—R₃₃ or —N(R₃₂)—SO₂R₃₄radical,

[0037] R₄ and R₃, which are identical or different, represent either anaromatic chosen from phenyl, naphthyl and indenyl, these aromatics beingunsubstituted or substituted by one or more halogen, alkyl, alkoxy,formyl, hydroxyl, trifluoromethyl, trifluoromethoxy, —CO-alk, cyano,—COOH, COOalk, —CONR₂₂R₂₃, —CO—NH—NR₂₄R₂₅, alkylsulfanyl, alkylsulfinyl,alkylsulfonyl, alkylsulfanylalkyl, alkylsulfinylalkyl,alkylsulfonylalkyl, hydroxyalkyl or -alk-NR₇R₈, or a heteroaromaticchosen from the benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl,chromanyl, 2,3-dihydrobenzofuryl, 2,3-dihydrobenzothienyl, furyl,imidazolyl, isochromanyl, isoquinolyl, pyrrolyl, pyridyl, pyrimidyl,quinolyl, 1,2,3,4-tetra-hydroisoquinolyl, thiazolyl and thienyl rings,it being possible for these heteroaromatics to be unsubstituted orsubstituted by a halogen, alkyl, alkoxy, hydroxyl, trifluoromethyl,trifluoromethoxy, cyano, —COOH, -COOalk, —CO—NH—NR₂₄R₂₅, —CONR₂₂R₂₃,-alk-NR₂₄R₂₅, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl,alkylsulfanylalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl orhydroxyalkyl,

[0038] R₃₂ represents a —C(R₃₅)(R₃₆)-Het₂, -Het₂, —C(R₃₅)(R₃₆)—Ar₂, Ar₂,cycloalkyl or norbornyl radical,

[0039] R₃₃ represents a hydrogen atom or a hydroxyalkyl, -alk-COOalk,-alk-CONR₂₂R₂₃, -alk-NR₂R₂₃, alkoxy, Ar₂, Het₂, —CH₂Ar₂, —CH₂Het₂ oralkyl radical, the latter optionally substituted by one or more halogen,

[0040] R₃₄ represents a hydroxyalkyl, -alk-COOalk, -alk-CONR₂₂R₂₃,-alk-NR₂₂R₂₃, alkoxy, Ar₂, Het₂, —CH₂Ar₂, —CH₂Het₂ or alkyl radical, thelatter optionally substituted by one or mote halogen,

[0041] R₃₅ represents a hydrogen atom or a hydroxyalkyl, -alk-COOalk,-alk-CONR₂₂R₂₃, -alk-NR₂₂R₂₃, alkoxyalkyl, Ar₂, Het₂, —CH₂Ar₂, —CH₂Het₂.or alkyl radical, the latter optionally substituted by one or morehalogen,

[0042] R₃₆ represents a hydrogen atom or a hydroxyalkyl, -alk-COOalk,-alk-CONR₂₂R₂₃, -alk-NR₂₂R₂₃, alkoxyalkyl or alkyl radical, the latteroptionally substituted by one or more halogen,

[0043] or else R₃₅ and R₃₆ form, together with the carbon atom to whichthey are attached, a saturated mono- or bicyclic ring having 3 to 10ring members optionally comprising another heteroatom chosen fromoxygen, sulfur and nitrogen and optionally being substituted by one ormore alkyl,

[0044] Ar₂ represents a phenyl, naphthyl or indenyl radical, thesevarious radicals optionally being substituted by one or more halogen,alkyl, alkoxy, —CO-alk, cyano, —COOH, —COOalk, —CONR₃₇R₃₈,—CO—NH—R₃₉R₄₀, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl,-alk-NR₃₉R₄₀, —NR₃₉R₄₀, alkylthioalkyl, formyl, CF₃, OCF₃, Het,-O-alk-NH-cycloalkyl, SO₂NH₂, hydroxyl, hydroxyalkyl, -NHCOalk orNHCOOalk or on 2 adjacent carbon atoms by dioxymethylene,

[0045] Het₂ represents an unsaturated or saturated mono- or bicyclicheterocycle having 3 to 10 ring members and comprising one or moreheteroatoms chosen from oxygen, sulfur and nitrogen which is optionallysubstituted by one or more alkyl, alkoxy, halogen, alkoxycarbonyl, oxoor hydroxyl, the nitrogenous heterocycles optionally being in theirN-oxidized form,

[0046] R₃₇ and R₃₈, which are identical or different, represent a.hydrogen atom or an alkyl radical or else R₃₇ and R₃₈ form, togetherwith the nitrogen atom to which they are attached, a saturated mono- orbicyclic heterocycle having 3 to 10 ring members optionally comprisinganother heteroatom chosen from oxygen, sulfur and nitrogen andoptionally being substituted by one or more alkyl,

[0047] R₃₉ and R₄₀, which are identical or different, represent ahydrogen atom or an alkyl radical or else R₃₉ and R₄₀ form, togetherwith the nitrogen atom to which they are attached, a saturated mono- orbicyclic heterocycle having 3 to 10 ring members optionally comprisinganother heteroatom chosen from oxygen, sulfur and nitrogen andoptionally being substituted by one or more alkyl,

[0048] alk represents an alkyl or alkylene radical,

[0049] the alkyl and alkylene radicals and portions and the alkoxyradicals and portions have straight or branched chains and comprise 1 to6 carbon atoms and the cycloalkyl radicals comprise 3 to 10 carbonatoms,

[0050] the optical isomers of these compounds and their pharmaceuticallyacceptable salts with an inorganic or organic acid.

[0051] The preferred azetidine derivatives are as follows:

[0052] 1-benzhydryl-3-[(methylsulfonyl)(phenyl) methylene]azetidine,

[0053]1-benzhydryl-3-[(3-methylphenyl)(methylsulfonyl)-methylene]azetidine,

[0054]1benzhydryl-3-[(3-chlorophenyl)(methylsulfonyl)-methylene]azetidine,

[0055]1-benzhydryl-3-[(3,5-dichlorophenyl)(methylsulfonyl)-methylene]azetidine,

[0056]1-benzhydryl-3-[(2,5-dichlorophenyl)(methylsulfonyl)-methylene]azetidine,

[0057]1-benzhydryl-3-[(2,3-dichlorophenyl)(methylsulfonyl)-methylene]azetidine,

[0058]1-benzhydryl-3-[(3-fluorophenyl)(methylsulfonyl)-methylene]azetidine,

[0059]1-benzhydryl-3-[(3,5-difluorophenyl)(methylsulfonyl)-methylene]azetidine,

[0060]1-benzhydryl-3-[(3-bromophenyl)(methylsulfonyl)-methylene]azetidine,

[0061]1-benzhydryl-3-[(3-iodophenyl)(methylsulfonyl)-methylene]azetidine,

[0062]1-benzhydryl-3-[(methylsulfonyl)(3-trifluoromethoxyphenyl)methylene]azetidine,

[0063]1-benzhydryl-3-[(methylsulfonyl)(3trifluoromethylphenyl)methylene]azetidine,

[0064]1-benzhydryl-3-{[3,5-bis(trifluoromethyl)phenyl]-(methylsulfonyl)methylene}azetidine,

[0065]1-benzhydryl-3-[(3,5-dibromophenyl)(methylsulfonyl)-methylene]azetidine,

[0066]1-benzhydryl-3-[(3-methoxycarbonylphenyl)-(methylsulfonyl)methylene]azetidine,

[0067]1-benzhydryl-3-[(3-cyanophenyl)(methylsulfonyl)-methylene]azetidine,

[0068]1-benzhydryl-3-[(3-carbamoylphenyl)(methylsulfonyl)-methylene]azetidine,

[0069]1-benzhydryl-3-[(methylsulfonyl)(naphth-1-yl)(methylsulfonyl)methylene]azetidine,

[0070]1-[bis(4-chlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)miethylene]azetidine,

[0071]1-[bis(4-methoxyphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0072]1-[bis(4-methylphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0073](RS)-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]-1-[(4-methoxyphenyl)(phenyl)methyl)]azetidine,

[0074](R)-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]-1-[(4-methoxyphenyl)(phenyl)methyl]azetidine,

[0075](S)-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]-1-[(4-methoxyphenyl)(phenyl)methyl]azetidine,

[0076]1-[bis(4-trifluoromethoxyphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0077]1-[bis(4-trifluoromethylphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0078]1-[bis(4-chlorophenyl)methyl]-3-{[3,5-bis(trifluoromethyl)phenyl]methylsulfonylmethylene}azetidine,

[0079](RS)-1-[(4-chlorophenyl)(2,4-dichlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)-methylene]azetidine,

[0080](R)-1-[(4-chlorophenyl)(2,4-dichlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)-methylene]azetidine,

[0081](S)-1-[(4-chlorophenyl)(2,4-dichlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0082](RS)-1-{(4-chlorophenyl)[4-(hydroxymethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0083](R)-1-{(4-chlorophenyl)[4-(hydroxymethyl)phenyl]methyl)-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0084](S)-1-{(4-chlorophenyl)[4-(hydroxymethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0085](RS)-1-{(4-chlorophenyl)[4-(pyrrolidylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0086](R)1-{(4-chlorophenyl)[4-(pyrrolidylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0087](S)-1{(4-chlorophenyl)[4-(pyrrolidylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0088] 1-(RS)-(4-chlorophenyl)[4-(3,3-dimethylpiperidin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0089]1-{(R)-(4-chlorophenyl)[4-(3,3-dimethylpiperidin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0090]1-{(S)-(4-chlorophenyl)[4-(3,3-dimethylpiperidin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0091]1-{(RS)-(4-chlorophenyl)[4-(thiomorpholin-4-ylmethyl)phenyl]methyl}-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0092]1-{(R)-(4-chlorophenyl)[4-(thiomorpholin-4-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0093]1-{(S)-(4-chlorophenyl)[4-(thiomorpholin-4-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0094]1-{(RS)-(4-chlorophenyl)[4-(N-ethyl-N-cyclohexylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0095]1-{(R)-(4-chlorophenyl)[4-(N-ethyl-N-cyclohexylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0096]1-{(S)-(4-chlorophenyl)[4-(N-ethyl-N-cyclohexylaminomethyl)phenyl]methyl)-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0097]1-{{(RS)-(4-chlorophenyl){4-[(4-ethoxycarbonylpiperazinyl)methyl]phenyl}methyl}}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0098]1-{{(R)-(4-chlorophenyl)(4-[(4-ethoxycarbonylpiperazinyl)methyl]phenyl}methyl)}}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0099]1-{{(S)-(4-chlorophenyl){4-[(4-ethoxycarbonylpiperazinyl)methyl]phenyl}methyl}}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0100]1-{(RS)-(4-chlorophenyl)[4-(N-cyclopropyl-N-propylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0101]1-{(R)(4-chlorophenyl)[4-(N-cyclopropyl-N-propylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0102]1-{(S)-(4-chlorophenyl)[4-(N-cyclopropyl-N-propylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0103] 1-{(RS)-(4-chlorophenyl)[4-(diisopropylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)-(methylsulfonyl)methylene]azetidine,

[0104]1-{(R)-(4-chlorophenyl)-[4-(diisopropylaminomethyl)-phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0105]1-{(S)-(4-chlorophenyl)[4-(diisopropylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)-methylene)azetidine,

[0106]1-{{(RS)-(4-chlorophenyl){4-[bis(2methoxyethyl)aminomethyl]phenyl}methyl}}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0107]1-{{(R)-(4-chlorophenyl){4-[bis(2-methoxyethyl)aminomethyl]phenyl}methyl}}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0108]1-{{(S)-(4-chlorophenyl){4-[his(2-methoxyethyl)aminomethyl]phenyl}methyl}}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0109]1-{(RS)-(4-chlorophenyl)[4-[di-n-propylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0110]1-{(R)-(4-chlorophenyl)[4-(di-n-propylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)-methylene]azetidine,

[0111]1-{(S)-(4-chlorophenyl)[4-(di-n-propylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0112] 1-{(RS)-(4-chlorophenyl)[4-(piperidin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0113]1-{(R)-(4-chlorophenyl)[4-(piperidin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0114]1-{(S)-(4-chlorophenyl)[4-(piperidin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0115]1-{(RS)-(4-chlorophenyl)[4-(4-methylpiperazin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0116]1-{(R)-(4-chlorophenyl)[4-(4-methylpiperazin-1-ylmethyl)phenyl]methyl}-3-1(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0117]1-{(S)-(4-chlorophenyl)[4-(4-methylpiperazin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0118]1-{(RS)-(4-chlorophenyl)[4-(morpholin-4-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0119]1-{(R)-(4-chlorophenyl)[4-(morpholin-4-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0120]1-{(S)-(4-chlorophenyl)[4-(morpholin-4-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0121]1-{(RS)-(4-chlorophenyl)(4-(diethylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0122]1-{(R)-(4-chlorophenyl)[4-(diethylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0123]1-{(S)-(4-chlorophenyl)[4-(diethylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0124]1-{((RS)-(4-chlorophenyl)[4-(piperazin-2-one-4-ylmethyl)pphenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0125]1{(R)-(4-chlorophenyl)[4-(piperazin-2-one-4-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0126]1-{(S)-(4-chlorophenyl)[4-(piperazin-2-one-4-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0127]1-{(RS)-(4-chlorophenyl)[4-(imidazol-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0128]1-{(R)-(4-chlorophenyl)[4-(imidazol-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0129]1-{(S)-(4-chlorophenyl)[4-(imidazol-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0130](RS)-1-{(4-chlorophenyl)[4-(N,N-dimethylcarbamoyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0131](R)-1-{(4-chlorophenyl)[4-(N,N-dimethylcarbamoyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0132](S)-1-{(4-chlorophenyl)[4-(N,N-dimethylcarbamoyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0133](RS)-1-{(4-chlorophenyl)[4-(N-ethylcarbarmoyl)phenyl]methyl)}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0134](R)-1-{(4-chlorophenyl)[4-(N-ethylcarbamoyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0135](S)1-{(4-chlorophenyl)[4-(N-ethylcarbamoyl)phenyl]methy}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0136](RS)-1-[(4-carbamoylphenyl)(4-chlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]-azetidine,

[0137](R)-1-[(4-carbamoylphenyl)(4-chlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]-azetidine,

[0138](S)-1-[(4-carbamoylphenyl)(4-chlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]-azetidine,

[0139]1-[bis(4-chlorophenyl)methyl]-3-[(3,5-dichlorophenyl)(methylsulfonyl)methylene]azetidine,

[0140]1-benzhydryl-3-[(3-methylsulfanylphenyl)(methylsulfonyl)methylene]azetidine,

[0141]1-benzhydryl-3-[(3-methylsulfanylmethyl)phenyl)]-(methylsulfonyl)methylene)azetidine,

[0142]1-[bis(4-chlorophenyl)methyl]-3-[(3-cyanophenyl)(methylsulfonyl)methylene]azetidine,

[0143]1-[bis(4-chlorophenyl)methyl]-3-[(3-carbamoylphenyl)(methylsulfonyl)methylene]azetidine,

[0144]1-[bis(4-chlorophenyl)methyl]-3-[(3-methoxyphenyl)(methylsulfonyl)methylene]azetidine,

[0145]1-[bis(4-chlorophenyl)methyl]-3-[(3-hydroxyphenyl)(methylsulfonyl)methylene]azetidine,

[0146]1-[bis(4-chlorophenyl)methyl]-3-[(methylsulfonyl)(3-pyrrolidinylphenyl)methylene]azetidine,

[0147]1-[bis(4-chlorophenyl)methyl]-3-[(3-hydroxymethylphenyl)(methylsulfonyl)methylene]azetidine,

[0148]1-[bis(4-chlorophenyl)methyl]-3-{(methylsulfonyl)[3-(N-piperidylcarbamoyl)phenyl]methylene}azetidine,

[0149]1-[bis(4-chlorophenyl)methyl]-3-[(methylsulfonyl)(3-trifluoromethylsulfanylphenyl)(methylsulfonyl)-methylene]azetidine,

[0150]1-[bis(4-fluorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0151]1-[bis(2-fluorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0152]1-[bis(3-fluorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0153](RS)-1-[(4-chlorophenyl)(thiazol-2-yl)methyl]-3-[(methylsulfonyl)(phenylmethylene]azetidine,

[0154](R)-1-[(4-chlorophenyl)(thiazol-2-yl)methyl]-3-[(methylsulfonyl)(phenyl)methylene]azetidine,

[0155](S)-1-f(4-chlorophenyl)(thiazol-2-yl)methyl)-3-[(methylsulfonyl)(phenyl)methylene]azetidine,

[0156](RS)-1-[(4-chlorophenyl)(thien-2-yl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0157](R)-1-[(4-chlorophenyl)(thien-2-yl)methyl]-3-[(3,5difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0158](S)-1-[(4-chlorophenyl)(thien-2-yl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0159] 1-benzhydryl-3-[(ethylsulfonyl)(phenyl)methylene]-azetidine,

[0160]1-[bis(4-chlorophenyl)methyl]3-{{3-[N-(4-methylpiperazinyl)carbamoyl]phenyl}(methylsulfonyl)methylene}azetidine,

[0161]1-[bis(4-chlorophenyl)methyl]3-{[3-(2,2-dimethylcarbohydrazido)phenyl](methylsulfonyl)methylene}azetidine,

[0162]1-[bis(thien-2-yl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0163]1-[bis(p-tolyl)methyl]-3-[(methylsulfonyl)(phenyl)methylene]azetidine,

[0164]1-[(4-chlorophenyl)(4-hydroxymethylphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]-azetidine,

[0165]1-[bis(4-chlorophenyl)methyl]-3-[(3-methylaminophenyl)(methylsulfonyl)methylene]azetidine,

[0166](RS)-1-[(4-chlorophenyl)(thiazol-2-yl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0167](R)-1-[(4-chlorophenyl)(thiazol-2-yl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0168](S)-1-[(4-chlorophenyl)(thiazol-2-yl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0169]1-[bis(4-chlorophenyl)methyl]-3-[(methylsulfonyl)(2-methoxycarbonylthien-5-yl)methylene]azetidine,

[0170](RS)-1-[[bis(4-chlorophenyl)methyl]-3-hydroxy-3-[(methylsulfonyl)(2-methoxycarbonylthien-5-yl)methyl]azetidine,

[0171]1-[bis(4-chlorophenyl)methyl]-3-[(2isobutylamino-carbonylthien-5-yl)(methylsulfonyl)methylene]azetidine,

[0172]1-[bis(4-chlorophenyl)methyl]-3-[(RS)-(3-methoxycarbonylphenyl)(methylsulfonyl)methyl]azetidin-3-ol,

[0173]1-[bis(4-chlorophenyl)methyl]-3-[(RS)-(methylsulfonyl)(pyridin-4-yl)methyl]azetidin-3-ol,

[0174]1-[{bis(4-chlorophenyl)methyl]-3-[(RS)-(methylsulfonyl)(pyridin-3-yl)methyl]azetidin-3-ol,

[0175]3-({1-[bis(4-chlorophenyl)methyl)azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(3-(morpholin-4-yl)propyl)benzamide,

[0176]3-({1[his(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(3-dimethylaminopropyl)benzamide,

[0177]3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-(pyrrolidin-1-yl)ethyl)benzamide,

[0178]3-({1-[bis(4-chlorophenyl)methyl)azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-dimethylamino-1-methylethyl)benzamide,

[0179]3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(piperidin-1-yl)benzamide,

[0180]3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-isobutylbenzamide,

[0181]3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(3-(imidazol-1-yl)propyl)benzamide,

[0182]3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-dimethylaminoethyl)benzamide,

[0183] N′-methylhydrazide of3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)-methyl)benzoicacid,

[0184]3-({1-[bis(4-chlorophenyl)methylazetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-(morpholin-4-yl)ethyl)benzamide,

[0185]3-({1-bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(1-ethylpyrrolidin-2-ylmethyl)benzamide,

[0186]3-({1-(bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2,2-dimethylpropyl)benzamide,

[0187]3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(cyclohexylmethyl)benzamide,

[0188]3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(cyclopropylmethyl)benzamide,

[0189]3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-methylbutyl)benzamide,

[0190]3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-phenylpropyl)benzamide,

[0191]3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(tetrahydrofuran-2-ylmethyl)benzamide,

[0192]3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2,2-diphenylethyl)benzamide,

[0193]3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-ethylbutyl)benzamide,

[0194] methyl ester of4-{[3-({1-[bis(4-chlorophenyl)methyl]-azetidin-3-ylidene}(methanesulfonyl)methyl}benzoylamino]methyl}cyclohexanecarboxylicacid,

[0195]2-amino-1-{4-(3-({1-(bis(4-chlorophenyl)methyl}-azetidin-3-ylidene)(methanesulfonyl)methyl)phenyl]-piperazin-1-yl}ethanone,

[0196] tert-butyl ester of(2-{4-[3-({1-[bis(4-chlorophenyl)-methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazin-1-yl}-2-oxoethyl)carbamicacid,

[0197]1-{4-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazin-1-yl}-2-(methylamino)ethanone,

[0198] tert-butyl ester of(2-{4-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazin-1-yl}-2-oxoethyl)-N-methylcarbamicacid,

[0199] N-methylamide of4-[3-({[1-bis(4-chlorophenyl)methylgazetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazine-1-carbothioicacid,

[0200] N-methylamide of4-[3-({1-[bis(4-chlorophenyl)methyl]-azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazine-1-carboxylicacid,

[0201] methyl ester of4-[3-({1-[bis(4-chlorophenyl)methyl]-azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazine-1-carboxylicacid,

[0202]1-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]-4-isobutylpiperazine,

[0203]1-[3-({1-[bis(4chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]-4-ethylpiperazine,

[0204]4-acetyl-1-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazine,

[0205]1-{4-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazin-1-yl}-2-dimethylaminoethanone,

[0206]1-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazine,

[0207] tert-butyl ester of4-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazine-1-carboxylicacid,

[0208]1-[bis(4-methoxycarbonylphenyl)methyl]3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0209]3-acetoxy-1-(bis(4-methoxycarbonylphenyl)methyl]-3-[(RS)-(3,5-difluorophenyl)(methylsulfonyl)methyl]-azetidine,

[0210](RS)-4-[4-((4-chlorophenyl){3-[(3,5-difluorophenyl)(methanesulfonyl)methylene]azetidin-1-yl}methyl)benzyl]morpholine,

[0211]4-(4-{3-[(1-benzhydrylazetidin-3-ylidene)(methanesulfonyl)methyl]phenoxy}butyl)morpholine,

[0212]4-(4-{3-[(1-benzhydrylazetidin-3-ylidene)(methanesulfonyl)methyl]phenoxy}propyl)morpholine,

[0213]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}thien-2-ylsulfonamide,

[0214]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-4-methoxyphenylsulfonamide,

[0215]N-[4-(N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}sulfamoyl)phenyl]acetamide,

[0216]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-4-methylphenylsulfonamide,

[0217]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3,4-dimethoxyphenylsulfonamide,

[0218]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3-fluorophenylsulfonamide,

[0219]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3,4-dichlorophenylsulfonamide,

[0220]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3-cyanophenylsulfonamide,

[0221]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-2,5-dimethoxyphenylsulfonamide,

[0222]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3-trifluoromethylphenylsulfonamide,

[0223]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}naphth-2-ylsulfonamide,

[0224]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}naphth-1-ylsulfonamide,

[0225]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3,4-difluorophenylsulfonamide,

[0226]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-1-methyl-1H-imidazol-4-ylsulfonamide,

[0227]N-[4-(N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}sulfamoyl)-2-chlorophenyl]acetamide,

[0228]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}pyrid-3-ylsulfonamide,

[0229]N-{1-[bis(4-chlorophenylmethyl]azetidin-3-yl}-4-fluorophenylsulfonamide,

[0230]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}quinol-8-ylsulfonamide,

[0231] N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}phenylsulfonamide,

[0232]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}(phenylmethyl)sulfonamide,

[0233]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3,5-difluorophenylsulfonamide,

[0234]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}pyrid-2-ylsulfonamide,

[0235]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-(3-fluoro-5-pyrrolidin-1-ylphenyl)sulfonamide,

[0236]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-methyl-4-fluorophenylsulfonamide,

[0237]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-methylquinol-8-ylsulfonamide,

[0238]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-methylphenylsulfonamide,

[0239]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-methyl(phenylmethyl)sulfonamide,

[0240]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3-sulfamoylphenylsulfonamide,

[0241]2-benzenesulfonyl-N-{1-[bis(4-chlorophenyl)methyl]-azetidin-3-yl}acetamide,

[0242]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-2-(4-toluene-4-sulfonyl)acetamide,

[0243](3-chloro-4-(methylsulfonyl)thiophene-2-carboxy)-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl]amide,

[0244]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3-(2-phenylethylenesulfonyl)propionamide,

[0245]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-4-(methylsulfonyl)benzamide,

[0246]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-4-(methanesulfonyl)benzamide,

[0247](5-(methylsulfonyl)thiophene-2-carboxy)-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}amide,

[0248](5-methylsulfonyl-3-methyl-4-vinylthiophene-2-carboxy){1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}amide,

[0249](RS)-N-{1-[(4-chlorophenyl)(pyridin-3-yl)methyl]-azetidin-3-yl}-3,5-difluorobenzenesulfonamide,

[0250](RS)-N-{1-[(4-chlorophenyl)(pyrimidin-5-yl)methyl]-azetidin-3-yl}-3,5-difluorobenzenesulfonamide,

[0251]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(6-chloropyrid-2-yl)methylsulfonamide,

[0252]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(6-ethylpyrid-2-yl)methylsulfonamide,

[0253]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(quinol-6-yl)methylsulfonamide,

[0254]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(quinol-5-yl)methylsulfonamide,

[0255]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(isoquinol-5-yl)methylsulfonamide,

[0256]N-{-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(pyrid-3-yl)methylsulfonamide,

[0257]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(pyrid-1-oxide-3-yl)methylsulfonamide,

[0258]N-(1R,2S,4S)-(bicyclo[2.2.1]hept-2-yl)-N-(1-[bis-(4-chlorophenyl)methylazetidin-3-yl)methylsulfonamide,

[0259]N-(1R,2R,4S)-(bicyclo[2.2.1]hept-2-yl)-N-{1-(bis-(4-chlorophenyl)methyl]azetidin-3-yl}methylsulfonamide,

[0260]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,

[0261]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(thiazol-2-yl)methylsulfonamide,

[0262]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3-methoxyphenyl)methylsulfonamide,

[0263]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3-hydroxyphenyl)methylsulfonamide,

[0264]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3-(hydroxymethyl)phenyl)methylsulfonamide,

[0265] ethylN-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(methylsulfonyl)-3-aminobenzoate,

[0266]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(isobutylpiperid-4-yl)methylsulfonamide,

[0267] N-benzyl-N-{1-[bis(4-chlorophenyl)methyl)azetidin-3-yl}amine,

[0268]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3,5-difluorobenzyl)amine,

[0269]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3,5-difluorobenzyl)methylsulfonamide,

[0270]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(pyrid-3-ylmethyl)methylsulfonamide,

[0271]N-{1-[bis(4-fluorophenyl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,

[0272](RS)-N-{1-[(4-chlorophenyl)(pyrid-3-yl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,

[0273](R)-N-{1-[(4-chlorophenyl)(pyrid-3-yl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,

[0274](S)-N-{1-[(4-chlorophenyl)(pyrid-3-yl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,

[0275](RS)-N-{1-[(4-chlorophenyl)(pyrid-4-yl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,

[0276](R)-N-{1-[(4-chlorophenyl)(pyrid-4-yl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,

[0277](S)-N-{1-[(4-chlorophenyl)(pyrid-4-yl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,

[0278](RS)-N-{1-[(4-chlorophenyl)(pyrimidin-5-yl)methyl]-azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,

[0279](R)-N-(1-[(4-chlorophenyl)(pyrimidin-5-yl)methyl]-azetidin-3-yl)-N-(3,5-difluorophenyl)methylsulfonamide,

[0280](S)-N-{1-[(4-chlorophenyl)(pyrimidin-5-yl)methyl]-azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,

[0281]N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)benzylsulfonamide,

[0282] their optical isomers and their pharmaceutically acceptable saltswith an inorganic or organic acid.

[0283] And even more particularly preferred are the following azetidinederivatives;

[0284]1-[bis(4-chlorophenyl)methyl]-3-[(RS)-(3,5-difluorophenyl)(methylsulfonyl)methyl]azetidin-3-ol,3-acetoxy-1-[bis(4-chlorophenyl)methyl]-3-[(RS)-(3,5-difluorophenyl)(methylulphonyl)methyl)methylsulfonylmethyl]azetidine,

[0285]1[bis(4-chlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

[0286] their optical isomers and their pharmaceutically acceptable saltswith an inorganic or organic acid.

[0287] Mention may be made, as examples of pharmaceutically acceptablesalts of the azetidine derivatives, of the following salts:benzenesulfonate, hydrobromide, hydrochloride, citrate, ethanesulfonate,fumarate, gluconate, iodate, isethionate, maleate, methanesulfonate,methylenebis-β-oxynaphthoate, nitrate, oxalate, pamoate, phosphate,salicylate, succinate, sulfate, tartrate, theophyllinacetate andp-toluenesulfonate.

[0288] Other CB1 [lacuna] antagonists of use in the combinationsaccording to the invention are, for example, the pyrazole derivativesdisclosed in EP 576 357, EP 658 546, EP 656 354, WO 97/19063 and WO00/46209, the benzothiophene and benzofuran derivatives disclosed in WO96/02248 or the arylsulfonamides disclosed in WO 98/37061. Mention mayin particular be made of the products known under the code SR141716 andLY320135.

[0289] The synergistic effect of the combination of sibutramine and of aCB1 [lacuna] antagonist on food intake was determined according to thefollowing protocol:

[0290] Obese Fa/fa Zucker rats aged 7 weeks and originating fromIffa-Credo, France, were used in this study. The rats are housed inindividual cages and weighed every day between 8 and 10 o'clock in themorning. The amount of food is also weighed each morning at the sametime. This food (M20, Pietrement, France) is changed every day and therats have free access thereto for 24 hours. All the rats are treated fora week with the vehicle (miglyol 812N and 0.5% methylcellulose/0.2%polysorbate 80) in two consecutive administrations. The rats are treatedfrom the 8th day with the vehicle, the Cal [lacuna] antagonist(1-[bis(4-dichlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine)or sibutramine by the oral route (see table below).

[0291] The sibutramine is dissolved an a 0.5% methylcellulose/0.2%polysorbate 80 solution and administered at a dose of 3 mg/kg; the CB1[lacuna] antagonist is dissolved in miglyol 812N (Hüls, Germany) at adose of 0.6 mg/kg and the two products are administered under a volumeof 1 ml/kg. Each group is composed of 12 to 14 animals. The followinggroups are formed and the animals are treated for five days at the rateof two consecutive administrations every day. First Second GROUPadministration administration 1 miglyol 0.5% methylcellulose/ “vehiclegroup” 0.2% polysorbate 2 miglyol sibutramine 3 mg/kg “sibutraminegroup” 3 CB1 [lacuna] 0.5% methylcellulose/ “CB1 [lacuna] antagonist0.2% polysorbate antagonist 0.6 mg/kg group” 4 CB1 [lacuna] sibutramine3 mg/kg “combination antagonist group” 0.6 mg/kg

[0292] The food consumption of each animal is measured every day. Theresults are expressed as mean amount of food consumed during the 5 daysof treatment. The results obtained are given in the table below. Foodconsumption during the Treatment 5 days of treatment (g) Vehicles 25.52± 0.30 sibutramine 3 mg/kg  24.60 ± 0.32* CB1 [lacuna] antagonist  24.00± 0.24** 0.6 mg/kg sibutramine (3 mg/kg) +   22.76 ± 0.02*** CB1[lacuna] antagonist (0.6 mg/kg)

[0293] The results show that, in'the animals receiving the sibutramineand CB1 [lacuna] antagonist combination, the reduction in foodconsumption is much greater has that of the animals treated either withsibutramine alone or with the CD1 [lacuna] antagonist alone.

[0294] The compounds of the combination can be employed orally,parenterally, transdermally or rectally, either simultaneously orseparately or spread out over time.

[0295] The present invention also relates to the pharmaceuticalcompositions comprising the combination of sibutramine, its hydrate orone of its pharmaceutically acceptable salts and of a CB1 receptorantagonist in the pure state or with one or more compatible andpharmacologically acceptable diluents and/or adjuvants and/or optionallyin combination with another pharmaceutically compatible andphysiologically active product for a use which is either simultaneous orseparate or spread out over time.

[0296] Use may be made, as solid compositions for oral administration,of tablets, pills, powders (hard gelatin capsules, cachets) or granules.In these compositions, the active principles are mixed with one or moreinert diluents, such as starch, cellulose, sucrose, lactose or silica,under an argon stream. These compositions can also comprise substancesother than the diluents, for example one or more lubricants such asmagnesium stearate or talc, a colorant, a coating (drages) or a glaze.

[0297] Use may be made, as liquid compositions for oral administration,of pharmaceutically acceptable solutions, suspensions, emulsions, syrupsand elixirs comprising inert diluents, such as water, ethanol, glycerol,vegetable oils or liquid paraffin. These compositions can comprisesubstances other than the diluents, for example wetting, sweetening,thickening, flavouring or stabilizing products.

[0298] The sterile compositions for parenteral administration canpreferably be solutions in aqueous or nonaqueous form, suspensions oremulsions. Use may be made, as solvent or vehicle, of water, propyleneglycol, a polyethylene glycol, vegetable oils, in particular olive oil,injectable organic esters, for example ethyl oleate, or other suitableorganic solvents. These compositions can also comprise adjuvants, inparticular wetting, isotonizing, emulsifying, dispersing and stabilizingagents. Sterilization can be carried out in several ways, for example byaseptic filtration, by incorporating sterilizing agents in thecomposition, by irradiation or by heating. They can also be prepared inthe form of sterile solid compositions which can be dissolved at thetime of use in sterile water or any other injectable sterile medium.

[0299] The compositions for rectal administration are suppositories orrectal capsules which comprise, in addition to the active product,excipients such as cocoa butter, semisynthetic glycerides orpolyethylene glycols.

[0300] The pharmaceutical compositions generally comprise 0.5 to 10 ragof sibutramine and 0.1 to 200 mg of the CB1 [lacuna] antagonist.

[0301] The present invention also relates to the method for thetreatment of obesity which consists in administering, to the patient, acombination according to the invention either simultaneously orseparately or spread out over time.

[0302] The doses depend on the desired effect, on the duration oftreatment and on the administration route used; they are generally from1 to 15 mg of sibutramine per day by the oral route for an adult andfrom 0.10 to 500 mg of the CB1 [lacuna] antagonist per day by the oralroute for an adult.

[0303] Generally, the doctor will determine the appropriate dosageaccording to the age, weight and any other factor specific to thesubject to be treated.

1. A combination of a CB1 [lacuna] antagonist and of sibutramine, itshydrate or one of its pharmaceutically acceptable salts.
 2. Thecombination as claimed in claim 1, for which the CB1 [lacuna] antagonistis a compound of formula:

in which either R represents a chain (A) or (B) and

R₁ represents a methyl or ethyl radical, R₂ represents either anaromatic chosen from phenyl, naphthyl or indenyl, these aromatics beingunsubstituted or substituted by one or more halogen, alkyl, alkoxy,—CO-alk, hydroxyl, —COOR₅, formyl, trifluoromethyl,trifluoromethylsulfanyl, trifluoromethoxy, nitro, —NR₆R₇, —CO—NH—NR₆R₇,—N(alk)COOR₈, cyano, —CONHR₉, —CO—NR₁₆R₁₇, alkylsulfanyl, hydroxyalkyl,—O-alk-NR₁₂R₁₃ or alkylthioalkyl, or a heteroaromatic chosen from thebenzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, chromanyl,2,3-dihydrobenzofuryl, 2,3-dihydrobenzothienyl, indolinyl, indolyl,isochromanyl, isoquinolyl, pyridyl, quinolyl,1,2,3,4-tetrahydroisoquinolyl, 1,2,3,4-tetrahydroquinolyl, thiazolyl orthienyl rings, it being possible for these heteroaromatics to beunsubstituted or substituted by a halogen, alkyl, alkoxy, —COOR₅,trifluoromethyl, trifluoromethylsulfanyl, trifluoromethoxy, nitro,—NR₆R₇, —CO—NH—NR₆R), cyano, —CONHR₉, alkylsulfanyl, hydroxyalkyl oralkylthioalkyl, R₃ and R₄, which are identical or different, representeither an aromatic chosen from phenyl, naphthyl or indenyl, thesearomatics being unsubstituted or substituted by one or more halogen,alkyl, alkoxy, formyl, hydroxyl, trifluoromethyl, trifluoromethoxy,—CO-alk, cyano, —COOR₅, —CONR₁₀R₁₁, —CO—NH—NR₆R₇, alkylsulfanyl,hydroxyalkyl, -alk-NR₆R₇ or alkylthioalkyl, or a heteroaromatic chosenfrom the benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl,chromanyl, 2,3-dihydrobenzofuryl, 2,3-dihydrobenzothienyl, furyl,isochromanyl, isoquinolyl, pyrrolyl, quinolyl,1,2,3,4-tetrahydroisoquinolyl, thiazolyl or thienyl rings, it beingpossible for these heteroaromatics to be unsubstituted or substituted bya halogen, alkyl, alkoxy, hydroxyl, trifluoromethyl, trifluoromethoxy,cyano, —COOR₅, —CO—NH—NR₆R₇, —CONR₁₀R₁₁, -alk-NR₆R₇, alkylsulfanyl,hydroxyalkyl or alkylthioalkyl, R₅ is an alkyl radical or a phenylradical optionally substituted by one or more halogen atoms, R₆ and R₇,which are identical or different, represent a hydrogen atom or an alkyl,-COOalk, cycloalkyl, alkylcycloalkyl, -alk-O-alk or hydroxyalkyl radicalor else R₆ and R₇ form, together with the nitrogen atom to which theyare attached, a saturated or unsaturated and mono- or bicyclicheterocycle having 3 to 10 ring members optionally comprising anotherheteroatom chosen from oxygen, sulfur and nitrogen and optionally beingsubstituted by one or more alkyl, -COalk, -COOalk, -CO-NHalk, -CS-NHalk,-CO-alk-NR₁₄R₁₅, oxo, hydroxyalkyl, -alk-O-alk or —CO—NH₂ radicals, R₈represents an alkyl radical, R₉ represents a hydrogen atom or a radicalof the type alkyl or alkyl substituted by dialkylamino, phenyl,cycloalkyl (optionally substituted by -COOalk) or a saturated orunsaturated and mono- or bicyclic heterocycle having 3 to 10 ringmembers optionally comprising one or more heteroatoms chosen fromoxygen, sulfur and nitrogen and optionally being substituted by one ormore alkyl radicals, R₁₀ and R₁₁, which are identical or different,represent a hydrogen atom or an alkyl radical or else R₁₀ and R₁₁ form,together with the nitrogen atom to which they are attached, a saturatedmono- or bicyclic heterocycle having 3 to 10 ring members optionallycomprising another heteroatom chosen from oxygen, sulfur and nitrogenand optionally being substituted by an alkyl radical, R₁₂ and R₁₃, whichare identical or different, represent a hydrogen atom or an alkyl orcycloalkyl radical or else R₁₂ and R₁₃ form, together with the nitrogenatom to which they are attached, a saturated mono- or bicyclicheterocycle having 3 to 10 ring members optionally comprising anotherheteroatom chosen from oxygen, sulfur and nitrogen and optionally beingsubstituted by an alkyl, -COalk, -COOalk, -CO-NHalk, -OS-NHalk or-CO-alk-NR₁₄R₁₅ radical or a saturated mono- or bicyclic heterocyclehaving 3 to 10 ring members and comprising a heteroatom chosen fromoxygen, sulfur and nitrogen, R₁₄ and R₁₅, which are identical ordifferent, represent a hydrogen atom or an alkyl or -COOalk radical, R₁₆and R₁₇ form, together with the nitrogen atom to which they areattached, a saturated mono- or bicyclic heterocycle having 3 to 10 ringmembers optionally comprising another heteroatom chosen from oxygen,sulfur and nitrogen, R′ represents a hydrogen atom or a -CO-alk radical,or R represents a CHR₁₈ radical and R₁₈ represents an —NHCOR₁₉ or—N(R₂₀)—Y—R₂₁ and Y is CO or SO₂, R₄ and R₃, which are identical ordifferent, represent either an aromatic chosen from phenyl, naphthyl andindenyl, these aromatics being unsubstituted or substituted by one ormore halogen, alkyl, alkoxy, formyl, hydroxyl, trifluoromethyl,trifluoromethoxy, -CO-alk, cyano, —COOH, -COOalk, —CONR₂₂R₂₃,—CO—NH—NR₂₄R₂₅, alkylsulfanyl, alkylsulfonyl, alkylsulfonyl,alkylsulfanylalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, hydroxyalkylor -alk-NH₂₂R₂₁, or a heteroaromatic chosen from the benzofuryl,benzothiazolyl, benzothienyl, benzoxazolyl, chromanyl,2,3-dihydrobenzofuryl, 2,3-dihydrobenzothienyl, pyrimidinyl, furyl,imidazolyl, isochromanyl, isoquinolyl, pyrrolyl, pyridyl, quinolyl,1,2,3,4-tetrahydroisoquinolyl, thiazolyl and thienyl rings, it beingpossible for these heteroaromatics to be unsubstituted or substituted bya halogen, alkyl, alkoxy, hydroxyl, trifluoromethyl, trifluoromethoxy,cyano, —COOH, -COOalk, —CO—NH—NR₂₄R₂₅, —CONR₂₂R₂₃, -alk-NR₂₄R₂₅,alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, alkylsulfanylalkyl,alkylsulfinylalkyl, alkylsulfonylalkyl or hydroxyalkyl, R₁₉ representsan -alk-SO₂-R₂₆ radical, an -alk-SO₂—CH═CH—R₂₆ radical, a Het₁ radicalsubstituted by —SO₂—R₂₅ or a phenyl radical substituted by —SO₂—R₂₆ or-alk-SO₂—R₂₆, R₂₀ represents a hydrogen atom or an alkyl radical, R₂₁represents a phenylalkyl, Het₁ or Ar₁ radical, R₂₂ and R₂₃, which areidentical or different, represent a hydrogen atom or an alkyl radical orelse R₂₂ and R₂₃ form, together with the nitrogen atom to which they areattached, a saturated mono- or bicyclic heterocycle having 3 to 10 ringmembers optionally comprising another heteroatom chosen from oxygen,sulfur and nitrogen and optionally being substituted by one or morealkyl, R₂₄ and R₂₅, which are identical or different, represent ahydrogen atom or an alkyl, -COOalk, cycloalkyl, alkylcycloalkyl,-alk-O-alk or hydroxyalkyl radical or else R₂₄ and R₂₅ form, togetherwith the nitrogen atom to which they are attached, a saturated orunsaturated mono- or bicyclic heterocycle having 3 to 10 ring membersoptionally comprising another heteroatom chosen from oxygen, sulfur andnitrogen and optionally being substituted by one or more alkyl, -COalk,-COOalk, -CO-NHalk, -CS-NHalk, oxo, hydroxyalkyl, -alk-O-alk or —CO—NH₂,R₂₆ represents an alkyl, Ar₁ or Het₁ radical, Ar₁ represents a phenyl,naphthyl or indenyl radical, these radicals optionally being substitutedby one or more halogen, alkyl, alkoxy, cyano, -CO-alk, -COOH, -COOalk,—CONR₂₇R₂₈, —CO—NH—NR₂₉R₃₀, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl,-alk-NR₂₉R₃₀, —NR₂₉R₃₀, alkylthioalkyl, formyl, hydroxyl, hydroxyalkyl,Het, -O-alk-NH-cycloalkyl, OCF₃, CF₃, —NH—CO-alk, —SO₂NH₂, —NH—COCH₃,-NH-COOalk or Het or else on 2 adjacent carbon atoms by dioxymethylene,Het₁ represents an unsaturated or saturated mono or bicyclic heterocyclehaving 3 to 10 ring members and comprising one or more heteroatomschosen from oxygen, sulfur and nitrogen which is optionally substitutedby one or more alkyl, alkoxy, vinyl, halogen, alkoxycarbonyl, oxo,hydroxyl, OCF₃ or CF₃, the nitrogenous heterocycles optionally being intheir N-oxidized form, R₂₇ and R₂₈, which are identical or different,represent a hydrogen atom or an alkyl radical or else R₂₇ and R₂₈ form,together with the nitrogen atom to which they are attached, a saturatedmono- or bicyclic heterocycle having 3 to 10 ring members optionallycomprising another heteroatom chosen from oxygen, sulfur and nitrogenand optionally being substituted by one or more alkyl radicals, R₂₉ andR₃₀, which are identical or different, represent a hydrogen atom or analkyl, -COOalk, cycloalkyl, alkylcycloalkyl, -alk-O-alk or hydroxyalkylradical or else R₂₉ and R₃₀ form, together with the nitrogen atom towhich they are attached, a saturated or unsaturated mono- or bicyclicheterocycle having 3 to 10 ring members optionally comprising anotherheteroatom chosen from oxygen, sulfur and nitrogen and optionally beingsubstituted by one or more alkyl, -COalk, -COOalk, -CO-NHalk, -CS-NHalk,oxo, hydroxyalkyl, -alk-O-alk or -CO-NH₂ radicals, or R represents CHR₃₁and R₃₁ represents an —N(R₃₂)R₃₃, —N(R₃₂)—CO—R₃₃ or —N(R₃₂)—SO₂R₃₄radical, R₄ and R₃, which are identical or different, represent eitheran aromatic chosen from phenyl, naphthyl and indenyl, these aromaticsbeing unsubstituted or substituted by one or more halogen, alkyl,alkoxy, formyl, hydroxyl, trifluoromethyl, trifluoromethoxy, -CO-alk,cyano, —COOH, COOalk, —CONR₂₂R₂₅, —CO—NH—NR₂₄R₂₅, alkylsulfanyl,alkylsulfinyl, alkylsulfonyl, alkylsulfanylalkyl, alkylsulfinylalkyl,alkylsulfonylalkyl, hydroxyalkyl or -alk-NR₇R₈, or a heteroaromaticchosen from the benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl,chromanyl, 2,3-dihydrobenzofuryl, 2,3-dihydrobenzothienyl, furyl,imidazolyl, isochromanyl, isoquinolyl, pyrrolyl, pyridyl, pyrimidyl,quinolyl, 1,2,3,4-tetra-hydroisoquinolyl, thiazolyl and thienyl rings,it being possible for these heteroaromatics to be unsubstituted orsubstituted by a halogen, alkyl, alkoxy, hydroxyl, trifluoromethyl,trifluoromethoxy, cyano, —COOH, -COOalk, —CO—NH—NR₂₄R₂₅, —CONR₂₂R₂₃,-alk-NR₂₄R₂₅, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl,alkylsulfanylalkyl, alkylsulfinylalkyl, alkyl sulfonylalkyl orhydroxyalkyl, R₃₂ represents a C(R₃₅) (R₃₆)-Het₂, -Het₂,—C(R₃₅)(R₃₆)—Ar₂, Ar₂, cycloalkyl or norbornyl radical, R₃₃ represents ahydrogen atom or a hydroxyalkyl, -alk-COOalk, -alk-CONR₂₂R₂₃,-alk-NR₂₂R₂₃, alkoxy, Ar₂, Het₂, —CH₂Ar₂, —CH₂Het₂ or alkyl radical, thelatter optionally substituted by one or more halogen, R₃₄ represents ahydroxyalkyl, -alk-COOalk, -alk-CONR₂₂R₂₃, -alk-NR₂₂R₂₃, alkoxy, Ar₂,Het₂, —CH₂Ar₂, -CH₂Het₂ or alkyl radical, the latter optionallysubstituted by one or more halogen, R₃₆ represents a hydrogen atom or ahydroxyalkyl, alk-COOalk, -alk-CONR₂₂R₂₃, -alk-NR₂₂R₂₃, alkoxyalkyl,Ar₂, Het₂, —CH₂Ar₂, —CH₂Het₂ or alkyl radical, the latter optionallysubstituted by one or more halogen, R₃₆ represents a hydrogen atom or ahydroxyalkyl, -alk-COOalk, -alk-CONR₂₂R₂₃, -alk-NR₂₂R₂₃, alkoxyalkyl oralkyl radical, the latter optionally substituted by one or more halogen,or else R₃₅ and R₃₅ form, together with the carbon atom to which theyare attached, a saturated mono- or bicyclic ring having 3 to 10 ringmembers optionally comprising another heteroatom chosen from oxygen,sulfur and nitrogen and optionally being substituted by one or morealkyl, Ar₂ represents a phenyl, naphthyl or indenyl radical, thesevarious radicals optionally being substituted by one or more halogen,alkyl, alkoxy, -CO-alk, cyano, —COOH, -COalk, —CONR₃₇R₃₈, —CO—NH—R₃₉R₄₀,alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, -alk-NR₃₉R₄₀, —NR₃₉R₄₀,alkylthioalkyl, formyl, CF₃, OCF₃, Het, -O-alkNH-cycloalkyl, SO₂NH₂,hydroxyl, hydroxyalkyl, -NHCOalk or NHOOalk or on 2 adjacent carbonatoms by dioxymethylene, Het₂ represents an unsaturated or saturatedmono- or bicyclic heterocycle having S to 10 ring members and comprisingone or more heteroatoms chosen from oxygen, sulfur and nitrogen which isoptionally substituted by one or more alkyl, alkoxy, halogen,alkoxycarbonyl, oxo or hydroxyl, the nitrogenous heterocycles optionallybeing in their N-oxidized form, R₃₇ and R₃₈, which are identical ordifferent, represent a hydrogen atom or an alkyl radical or else R₃₇ andR₃₈ form, together with the nitrogen atom to which they are attached, asaturated mono- or bicyclic heterocycle having 3 to 10 ring membersoptionally comprising another heteroatom chosen from oxygen, sulfur andnitrogen and optionally being substituted by one or more alkyl, R₃₉ andR₄₀, which are identical or different, represent a hydrogen atom or analkyl radical or else R₃₉ and R₄₀ form, together with the nitrogen atomto which they are attached, a saturated mono- or bicyclic heterocyclehaving 3 to 10 ring members optionally comprising another heteroatomchosen from oxygen, sulfur and nitrogen and optionally being substitutedby one or more alkyl, alk represents an alkyl or alkylene radical, thealkyl and alkylene radicals and portions and the alkoxy radicals andportions have straight or branched chains and comprise 1 to 6 carbonatoms and the cycloalkyl radicals comprise 3 to 10 carbon atoms, theoptical isomers of these compounds and their pharmaceutically acceptablesalts with an inorganic or organic acid.
 3. The combination as claimedin claim 2, for which the compound of formula (I) is chosen from thefollowing compounds:1-benzhydryl-3-[(methylsulfonyl)(phenyl)methylene]azetidine,1-benzhydryl-3-[(3-methylphenyl)(methylsulfonyl)-methylene]azetidine,1benzhydryl-3-[(3-chlorophenyl)(methylsulfonyl)-methylene]azetidine,1-benzhydryl-3-[(3,5-dichlorophenyl)(methylsulfonyl)-methylene]azetidine,1-benzhydryl-3-[(2,5-dichlorophenyl)(methylsulfonyl)-methylene]azetidine,1-benzhydryl-3-[(2,3-dichlorophenyl)(methylsulfonyl)-methylene]azetidine,1-benzhydryl-3-[(3-fluorophenyl)(methylsulfonyl)-methylene]azetidine,1-benzhydryl-3-1(3,5-difluorophenyl)(methylsulfonyl)-methylene]azetidine,1-benzhydryl-3-[(3-bromophenyl)(methylsulfonyl)-methylene]azetidine,1-benzhydryl-3-[(3-iodophenyl)(methylsulfonyl)-methylene]azetidine,1-benzhydryl-3-[(methylsulfonyl)(3-trifluoromethoxyphenyl)methylene]azetidine,1-benzhydryl-3-[(methylsulfonyl)(3trifluoromethylphenyl)methylene]azetidine,1-benzhydryl-3-{[3,5-bis(trifluoromethyl)phenyl]-(methylsulfonyl)methylene}azetidine,1-benzhydryl-3-[(3,5-dibromophenyl)(methylsulfonyl)-methylene]azetidine,1-benzhydryl-3-[(3-methoxycarbonylphenyl)-(methylsulfonyl)methylene]azetidine,1-benzhydryl-3-[(3-cyanophenyl)(methylsulfonyl)-methylene]azetidine,1-benzhydryl-3-[(3-carbamoylphenyl)(methylsulfonyl)-methylene]azetidine,1-benzhydryl-3-[(methylsulfonyl)(naphth-1-yl)(methylsulfonyl)methylene]azetidine,1-[bis(4-chlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)miethylene]azetidine,1-[bis(4-methoxyphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-[bis(4-methylphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(RS)-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]-1-[(4-methoxyphenyl)(phenyl)methyl)]azetidine,(R)-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]-1-[(4-methoxyphenyl)(phenyl)methyl]azetidine,(S)-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]-1-[(4-methoxyphenyl)(phenyl)methyl]azetidine,1-[bis(4-trifluoromethoxyphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-[bis(4-trifluoromethylphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-[bis(4-chlorophenyl)methyl]-3-{[3,5-bis(trifluoromethyl)phenyl]methylsulfonylmethylene}azetidine,(RS)-1-[(4-chlorophenyl)(2,4-dichlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)-methylene]azetidine,(R)-1-[(4-chlorophenyl)(2,4-dichlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)-methylene]azetidine,(S)-1-[(4-chlorophenyl)(2,4-dichlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(RS)-1-{(4-chlorophenyl)[4-(hydroxymethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(R)-1-{(4-chlorophenyl)[4-(hydroxymethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(S)-1-{(4-chlorophenyl)[4-(hydroxymethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(RS)-1-{(4-chlorophenyl)[4-(pyrrolidylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(R)1-{(4-chlorophenyl)[4-(pyrrolidylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(S)-1{(4-chlorophenyl)[4-(pyrrolidylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(RS)-(4-chlorophenyl)[4-(3,3-dimethylpiperidin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(R)-(4-chlorophenyl)[4-(3,3-dimethylpiperidin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(S)-(4-chlorophenyl)[4-(3,3-dimethylpiperidin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(RS)-(4-chlorophenyl)[4-(thiomorpholin-4-ylmethyl)phenyl]methyl}-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(R)-(4-chlorophenyl)[4-(thiomorpholin-4-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(S)-(4-chlorophenyl)[4-(thiomorpholin-4-ylmthyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(RS)-(4-chlorophenyl)[4-(N-ethyl-N-cyclohexylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(R)-(4-chlorophenyl)[4-(N-ethyl-N-cyclohexylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(S)-(4-chlorophenyl)[4-(N-ethyl-N-cyclohexylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{{(RS)-(4-chlorophenyl){4-[(4-ethoxycarbonylpiperazinyl)methyl]phenyl}methyl}}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{{(R)-(4-chlorophenyl){4-[(4-ethoxycarbonylpiperazinyl)methyl]phenyl}methyl)}}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{{(S)-(4-chlorophenyl){4-[(4-ethoxycarbonylpiperazinyl)methyl]phenyl}methyl}}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(RS)-(4-chlorophenyl)[4-(N-cyclopropyl-N-propylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(R)(4-chlorophenyl)[4-(N-cyclopropyl-N-propylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(S)-(4-chlorophenyl)[4-(N-cyclopropyl-N-propylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(RS)-(4-chlorophenyl)[4-(diisopropylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)-(methylsulfonyl)methylene]azetidine,1-{(R)-(4-chlorophenyl)[4-(diisopropylaminomethyl)-phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(S)-(4-chlorophenyl)[4-(diisopropylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)-methylene)azetidine,1-{{(RS)-(4-chlorophenyl){4-[bis(2methoxyethyl)aminomethyl]phenyl}methyl}}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{{(R)-(4-chlorophenyl){4-[bis(2-methoxyethyl)aminomethyl]phenyl}methyl}}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{{(S)-(4-chlorophenyl){4-[his(2-methoxyethyl)aminomethyl]phenyl}methyl}}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(RS)-(4-chlorophenyl)[4-[di-n-propylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(R)-(4-chlorophenyl)[4-(di-n-propylaminomethyl)phenyl]methyl}-3-1(3,5-difluorophenyl)(methylsulfonyl)-methylene]azetidine,1-{(S)-(4-chlorophenyl)[4-(di-n-propylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(RS)-(4-chlorophenyl)[4-(piperidin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(R)-(4-chlorophenyl)[4-(piperidin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(S)-(4-chlorophenyl)[4-(piperidin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(RS)-(4-chlorophenyl)[4-(4-methylpiperazin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(R)-(4-chlorophenyl)[4-(4-methylpiperazin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(S)-(4-chlorophenyl)[4-(4-methylpiperazin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(RS)-(4-chlorophenyl)[4-(morpholin-4-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(R)-(4-chlorophenyl)[4-(morpholin-4-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(S)-(4-chlorophenyl)[4-(morpholin-4-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(RS)-(4-chlorophenyl)(4-(diethylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(R)-(4-chlorophenyl)[4-(diethylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(S)-(4-chlorophenyl)[4-(diethylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(RS)-(4-chlorophenyl)[4-(piperazin-2-one-4-ylmethyl)pphenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1{(R)-(4-chlorophenyl)[4-(piperazin-2-one-4-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(S)-(4-chlorophenyl)[4-(piperazin-2-one-4-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(RS)-(4-chlorophenyl)[4-(imidazol-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(R)-(4-chlorophenyl)[4-(imidazol-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(S)-(4-chlorophenyl)[4-(imidazol-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(RS)-1-{(4-chlorophenyl)[4-(N,N-dimethylcarbamoyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(R)-1-{(4-chlorophenyl)[4-(N,N-dimethylcarbamoyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(S)-1-{(4-chlorophenyl)[4-(N,N-dimethylcarbamoyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(RS)-1-{(4-chlorophenyl)[4-(N-ethylcarbarmoyl)phenyl]methyl)}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(R)-1-{(4-chlorophenyl)[4-(N-ethylcarbamoyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(S)1-{(4-chlorophenyl)[4-(N-ethylcarbamoyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(RS)-1-[(4-carbamoylphenyl)(4-chlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]-azetidine,(R)-1-[(4-carbamoylphenyl)(4-chlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]-azetidine,(S)-1-[(4-carbamoylphenyl)(4-chlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]-azetidine,1-[bis(4-chlorophenyl)methyl]-3-[(3,5-dichlorophenyl)(methylsulfonyl)methylene]azetidine,1-benzhydryl-3-[(3-methylsulfanylphenyl)(methylsulfonyl)methylene]azetidine,1-benzhydryl-3-[(3-methylsulfanylmethyl)phenyl)]-(methylsulfonyl)methylene)azetidine,1-[bis(4-chlorophenyl)methyl]-3-[(3-cyanophenyl)(methylsulfonyl)methylene]azetidine,1-[bis(4-chlorophenyl)methyl]-3-[(3-carbamoylphenyl)(methylsulfonyl)methylene]azetidine,1-[bis(4-chlorophenyl)methyl]-3-[(3-methoxyphenyl)(methylsulfonyl)methylene]azetidine,1-[bis(4-chlorophenyl)methyl]-3-[(3-hydroxyphenyl)(methylsulfonyl)methylene]azetidine,1-[bis(4-chlorophenyl)methyl]-3-[(methylsulfonyl)(3-pyrrolidinylphenyl)methylene]azetidine,1-[bis(4-chlorophenyl)methyl]-3-[(3-hydroxymethylphenyl)(methylsulfonyl)methylene]azetidine,1-[bis(4-chlorophenyl)methyl]-3-{(methylsulfonyl)[3-(N-piperidylcarbamoyl)phenyl]methylene}azetidine,1-[bis(4-chlorophenyl)methyl]-3-[(methylsulfonyl)(3-trifluoromethylsulfanylphenyl)(methylsulfonyl)-methylene]azetidine,1-[bis(4-fluorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-[bis(2-fluorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-[bis(3-fluorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(RS)-1-[(4-chlorophenyl)(thiazol-2-yl)methyl]-3-[(methylsulfonyl)(phenylmethylene]azetidine,(R)-1-[(4-chlorophenyl)(thiazol-2-yl)methyl]-3-[(methylsulfonyl)(phenyl)methylene]azetidine,(S)-1-[(4-chlorophenyl)(thiazol-2-yl)methyl]-3-[(methylsulfonyl)(phenyl)methylene]azetidine,(RS)-1-[(4-chlorophenyl)(thien-2-yl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(R)-1-[(4-chlorophenyl)(thien-2-yl)methyl]-3-[(3,5difluorophenyl)(methylsulfonyl)methylene]azetidine,(S)-1-[(4-chlorophenyl)(thien-2-yl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-benzhydryl-3-[(ethylsulfonyl)(phenyl)methylene]-azetidine,1-[bis(4-chlorophenyl)methyl]3-{{3-[N-(4-methylpiperazinyl)carbamoyl]phenyl}(methylsulfonyl)methylene}azetidine,1-[bis(4-chlorophenyl)methyl]3-{[3-(2,2-dimethylcarbohydrazido)phenyl](methylsulfonyl)methylene}azetidine,1-[bis(thien-2-yl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-[bis(p-tolyl)methyl]-3-[(methylsulfonyl)(phenyl)methylene]azetidine,1-[(4-chlorophenyl)(4-hydroxymethylphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]-azetidine,1-[bis(4-chlorophenyl)methyl]-3-[(3-methylaminophenyl)(methylsulfonyl)methylene]azetidine,(RS)-1-[(4-chlorophenyl)(thiazol-2-yl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(R)-1-[(4-chlorophenyl)(thiazol-2-yl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(S)-1-[(4-chlorophenyl)(thiazol-2-yl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-[bis(4-chlorophenyl)methyl]-3-[(methylsulfonyl)(2-methoxycarbonylthien-5-yl)methylene]azetidine,(RS)-1-[bis(4-chlorophenyl)methyl]-3-hydroxy-3-[(methylsulfonyl)(2-methoxycarbonylthien-5-yl)methyl]azetidine,1-[bis(4-chlorophenyl)methyl]-3-[(2isobutylamino-carbonylthien-5-yl)(methylsulfonyl)methylene]azetidine,1-[bis(4-chlorophenyl)methyl]-3-[(RS)-(3-methoxycarbonylphenyl)(methylsulfonyl)methyl]azetidin-3-ol,1-[bis(4-chlorophenyl)methyl]-3-[(RS)-(methylsulfonyl)(pyridin-4-yl)methyl]azetidin-3-ol,1-[bis(4-chlorophenyl)methyl)-3-[(RS)-(methylsulfonyl)(pyridin-3-yl)methyl]azetidin-3-ol,3-({1-[bis(4-chlorophenyl)methyl)azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(3-(morpholin-4-yl)propyl)benzamide,3-({1[his(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(3-dimethylaminopropyl)benzamide,3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-(pyrrolidin-1-yl)ethyl)benzamide,3-({1-[bis(4-chlorophenyl)methyl)azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-dimethylamino-1-methylethyl)benzamide,3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(piperidin-1-yl)benzamide,3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-isobutylbenzamide,3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(3-(imidazol-1-yl)propyl)benzamide,3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-dimethylaminoethyl)benzamide,N′-methylhydrazide of3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)-methyl)benzoicacid,3-({1-[bis(4-chlorophenyl)methylazetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-(morpholin-4-yl)ethyl)benzamide,3-({1-bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(1-ethylpyrrolidin-2-ylmethyl)benzamide,3-({1-(bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2,2-dimethylpropyl)benzamide,3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(cyclohexylmethyl)benzamide,3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(cyclopropylmethyl)benzamide,3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-methylbutyl)benzamide,3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-phenylpropyl)benzamide,3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(tetrahydrofuran-2-ylmethyl)benzamide,3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2,2-diphenylethyl)benzamide,3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-ethylbutyl)benzamide,methyl ester of4-{[3-({1-[bis(4-chlorophenyl)methyl]-azetidin-3-ylidene}(methanesulfonyl)methyl)benzoylamino]methyl}cyclohexanecarboxylicacid,2-amino-1-{4-(3-({1-(bis(4-chlorophenyl)methyl]-azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]-piperazin-1-yl}ethanone,tert-butyl ester of(2-{4-[3-({1-[bis(4-chlorophenyl)-methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazin-1-yl}-2-oxoethyl)carbamicacid,1-{4-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazin-1-yl}-2-(methylamino)ethanone,tert-butyl ester of(2-{4-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazin-1-yl}-2-oxoethyl)-N-methylcarbamicacid, N-methylamide of4-[3-({[1-bis(4-chlorophenyl)methylgazetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazine-1-carbothioicacid, N-methylamide of4-[3-({1-[bis(4-chlorophenyl)methyl]-azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazine-1-carboxylicacid, methyl ester of4-[3-({1-[bis(4-chlorophenyl)methyl]-azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazine-1-carboxylicacid,1-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]-4-isobutylpiperazine,1-[3-({1-[bis(4chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]-4-ethylpiperazine,4-acetyl-1-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazine,1-{4-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazin-1-yl}-2-dimethylaminoethanone,1-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazine,tert-butyl ester of4-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazine-1-carboxylicacid,1-[bis(4-methoxycarbonylphenyl)methyl]3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,3-acetoxy-1-[bis(4-methoxycarbonylphenyl)methyl]-3-[(RS)-(3,5-difluorophenyl)(methylsulfonyl)methyl]-azetidine,(RS)-4-[4-((4-chlorophenyl){3-[(3,5-difluorophenyl)(methanesulfonyl)methylene]azetidin-1-yl}methyl)benzyl]morpholine,4-(4-{3-[(1-benzhydrylazetidin-3-ylidene)(methanesulfonyl)methyl]phenoxy}butyl)morpholine,4-(4-{3-[(1-benzhydrylazetidin-3-ylidene)(methanesulfonyl)methyl]phenoxy}propyl)morpholine,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}thien-2-ylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-4-methoxyphenylsulfonamide,N-[4-(N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}sulfamoyl)phenyl]acetamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-4-methylphenylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3,4-dimethoxyphenylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3-fluorophenylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3,4-dichlorophenylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3-cyanophenylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-2,5-dimethoxyphenylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3-trifluoromethylphenylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}naphth-2-ylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}naphth-1-ylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3,4-difluorophenylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-1-methyl-1H-imidazol-4-ylsulfonamide,N-[4-(N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}sulfamoyl)-2-chlorophenyl]acetamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}pyrid-3-ylsulfonamide,N-{1-[bis(4-chlorophenylmethyl]azetidin-3-yl}-4-fluorophenylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}quinol-8-ylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}phenylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}(phenylmethyl)sulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3,5-difluorophenylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}pyrid-2-ylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-(3-fluoro-5-pyrrolidin-1-ylphenyl)sulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-methyl-4-fluorophenylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-methylquinol-8-ylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-methylphenylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-methyl(phenylmethyl)sulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3-sulfamoylphenylsulfonamide,2-benzenesulfonyl-N-{1-[bis(4-chlorophenyl)methyl]-azetidin-3-yl}acetamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-2-(4-toluene-4-sulfonyl)acetamide,(3-chloro-4-(methylsulfonyl)thiophene-2-carboxy)-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl]amide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3-(2-phenylethylenesulfonyl)propionamide,N-[1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-4-(methylsulfonyl)benzamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-4-(methanesulfonyl)benzamide,(5-(methylsulfonyl)thiophene-2-carboxy)-{1-[bis(4-chlorophenyl)methylazetidin-3-yl}amide,(5-methylsulfonyl-3-methyl-4-vinylthiophene-2-carboxy){1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}amide,(RS)-N-{1-[(4-chlorophenyl)(pyridin-3-yl)methyl]-azetidin-3-yl}-3,5-difluorobenzenesulfonamide,(RS)-N-{1-[(4-chlorophenyl)(pyrimidin-5-yl)methyl]-azetidin-3-yl}-3,5-difluorobenzenesulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(6-chloropyrid-2-yl)methylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(6-ethylpyrid-2-yl)methylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(quinol-6-yl)methylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(quinol-5-yl)methylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(isoquinol-5-yl)methylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(pyrid-3-yl)methylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(pyrid-1-oxide-3-yl)methylsulfonamide,N-(1R,2S,4S)-(bicyclo[2.2.1]hept-2-yl)-N-(1-[bis-(4-chlorophenyl)methylazetidin-3-yl)methylsulfonamide,N-(1R,2R,4S)-(bicyclo[2.2.1]hept-2-yl)-N-{1-(bis-(4-chlorophenyl)methyl]azetidin-3-yl}methylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(thiazol-2-yl)methylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3-methoxyphenyl)methylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3-hydroxyphenyl)methylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3-(hydroxymethyl)phenyl)methylsulfonamide,ethylN-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(methylsulfonyl)-3-aminobenzoate,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(isobutylpiperid-4-yl)methylsulfonamide,N-benzyl-N-{1-[bis(4-chlorophenyl)methyl)azetidin-3-yl}amine,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3,5-difluorobenzyl)amine,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3,5-difluorobenzyl)methylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(pyrid-3-ylmethyl)methylsulfonamide,N-{1-[bis(4-fluorophenyl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,(RS)-N-{1-[(4-chlorophenyl)(pyrid-3-yl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,(R)-N-{1-[(4-chlorophenyl)(pyrid-3-yl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,(S)-N-{1-[(4-chlorophenyl)(pyrid-3-yl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,(RS)-N-{1-[(4-chlorophenyl)(pyrid-4-yl)methyl]azetidin-3-yl)-N-(3,5-difluorophenyl)methylsulfonamide,(R)-N-{1-[(4-chlorophenyl)(pyrid-4-yl)methyl}azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,(S)-N-{1-[(4-chlorophenyl)(pyrid-4-yl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,(RS)-N-{1-[(4-chlorophenyl)(pyrimidin-5-yl)methyl]-azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,(R)-N-(1-[(4-chlorophenyl)(pyrimidin-5-yl)methyl]-azetidin-3-yl)-N-(3,5-difluorophenyl)methylsulfonamide,(S)-N-{1-[(4-chlorophenyl)(pyrimidin-5-yl)methyl]-azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)benzylsulfonamide,their optical isomers and their pharmaceutically acceptable salts. 4.The combination as claimed in claim 2, for which the compound of formula(I) is chosen from 1.5 the following compounds:1-[bis(4-chlorophenyl)methyl]-3-[(RS)-(3,5-difluorophenyl)(methylsulfonyl)methyl]azetidin-3-ol,3-acetoxy-1-[bis(4-chlorophenyl)methyl]-3-[(RS)-(3,5-difluorophenyl)(methylulphonyl)methyl)methylsulfonyl-methylazetidine,1-[bis(4-chlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,their optical isomers and their pharmaceutically acceptable salts. 5.The combination as claimed in claim 1, in which the CB1 [lacuna]antagonist is SR141716, its hydrates and its pharmaceutically acceptablesalts or LY320135 and its pharmaceutically acceptable salts.
 6. Apharmaceutical composition comprising a CE1 [lacuna] antagonist andsibutramine, its hydrate or one of its pharmaceutically acceptable saltsin the pure state ox with one or more compatible and pharmacologicallyacceptable diluents and/or adjuvants and/or optionally in combinationwith another pharmaceutically compatible and physiologically activeproduct.
 7. The pharmaceutical composition as claimed in claim 6, forwhich the CB1 [lacuna] antagonist [lacuna] of formula I as defined inclaim
 2. 8. The pharmaceutical composition as claimed in claim 7, forwhich the compound of formula (1) is chosen from the followingcompounds: 1-benzhydryl-3-[(methylsulfonyl)(phenyl)methylene]azetidine,1-benzhydryl-3-[(3-methylphenyl)(methylsulfonyl)-methylene]azetidine,1-benzhydryl-3-[(3-chlorophenyl)(methylsulfonyl)-methylene]azetidine,1-benzhydryl-3-[(3,5-dichlorophenyl)(methylsulfonyl)-methylene]azetidine,1-benzhydryl-3-[(2,5-dichlorophenyl)(methylsulfonyl)-methylene]azetidine,1-benzhydryl-3-[(2,3-dichlorophenyl)(methylsulfonyl)-methylene]azetidine,1-benzhydryl-3-[(3-fluorophenyl)(methylsulfonyl)-methylene]azetidine,1-benzhydryl-3-[(3,5-difluorophenyl)(methylsulfonyl)-methylene]azetidine,1-benzhydryl-3-[(3bromophenyl)(methylsulfonyl)-methylene]azetidine,1-benzhydryl-3-[(3-iodophenyl)(methylsulfonyl)-methylene]azetidine,1-benzhydryl-2-[(methylsulfonyl)(3-trifluoromethoxyphenyl)methylene]azetidine,1-benzhydryl-3-[(methylsulfonyl)(3-trifluoromethylphenyl)methylene]azetidine,1-benzhydryl-3-{[3,5-bis(trifluoromethyl)phenyl]-(methylsulfonyl)methylene}azetidine,1-benzhydryl-3-[(3,5-dibromophenyl)(methylsulfonyl)-methylene]azetidine,1-benzhydryl-3-[(3-methoxycarbonylphenyl)(methylsulfonyl)methylene]azetidine,1-benzhydryl-3-[(3-cyanophenyl)(methylsulfonyl)-methylene]azetidine,1-benzhydryl-3-[(3-carbamoylphenyl)(methylsulfonyl)-methylene]azetidine,1-benzhydryl-3-[(methylsulfonyl)(naphth-1-yl)(methylsulfonyl)methylene]azetidine,1-[bis(4-chlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-[bis(4-methoxyphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-[bis(4-methylphenylmethyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(RS)-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]-1-[(4-methoxyphenyl)(phenyl)methyl)]azetidine,(R)-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]-3-1-1(4-methoxyphenyl)(phenyl)methyl]azetidine,(S)-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]-1-[(4-methoxyphenyl)(phenyl)methyl]azetidine,1-[bis(4-trifluoromethoxyphenyl)methyl-1-3-[(3,5-di-fluorophenyl)(methylsulfonyl)methylene]azetidine,1-[bis(4-trifluoromethylphenyl)methyl]-3-[(3,5-di-fluorophenyl)(methylsulfonyl)methylene]azetidine,1-[bis(4-chlorophenyl)methyl]-3-{[3,5-bis(trifluoromethyl)phenyl]methylsulfonylmethylene}azetidine,(RS)-1-[(4-chlorophenyl)(2,4-dichlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(R)-1-[(4-chlorophenyl)(2,4-dichlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)ethylene]azetidine,(S)-1[(4-chlorophenyl)(2,4-dichlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)ethylene]azetidine,(RS)-1-{(4-chlorophenyl)[4-(hydroxymethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(R)-1-{(4-chlorophenyl)[4-(hydroxymethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(S)-1{(4-chlorophenyl)[4-(hydroxymethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methymene]azetidine,(RS)-1-{(4-chlorophenyl)[4-(pyrrolidylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(R)-1-{(4-chlorophenyl)[4-(pyrrolidylmethyl)phenyl]methyl}-3[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(S)-1-{(4-chlorophenyl)[4-(pyrrolidylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(RS)-(4-chlorophenyl)[4-(3,3-dimethylpiperidin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(R)-(4-chlorophenyl)[4-(3,3-dimethylpiperidin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(S)-(4-chlorophenyl)[4-(3,3-dimethylpiperidin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(RS)-(4-chlorophenyl)[4-(thiomorpholin-4-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(R)-(4-chlorophenyl)[4-(thiomorpholin-4-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(S)-(4-chlorophenyl)[4-(thiomorpholin-4-ylmthyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(RS)-(4-chlorophenyl)[4-(N-ethyl-N-cyclohexylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(R)-(4-chlorophenyl)[4-(N-ethyl-N-cyclohexylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(S)-(4-chlorophenyl)[4-(N-ethyl-N-cyclohexylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{{(RS)-(4-chlorophenyl){4-[(4-ethoxycarbonylpiperazinyl)methyl]phenyl}methyl}}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{{(R)-(4-chlorophenyl){4-[(4-ethoxycarbonylpiperazinyl)methyl]phenyl}methyl}}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{{(S)-(4-chlorophenyl){4-[(4-ethoxycarbonylpiperazinyl)methyl]phenyl}methyl}}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(RS)-(4-chlorophenyl)[4-(N-cyclopropyl-N-propylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(R)-(4-chlorophenyl)[4-(N-cyclopropyl-N-propylaminomethyl)phenyl]methyl}3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(S)-(4-chlorophenyl)[4-(N-cyclopropyl-N-propylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(RS)-((4-chlorophenyl)[4-(diisopropylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(R)-(4-chlorophenyl)[4-(diisopropylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(S)-(4-chlorophenyl)14-(diisopropylaminomethyl)phenyl]methyl}-3-1(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{{(RS)-(4-chlorophenyl){4-[bis(2-methoxyethyl)aminomethyl]phenyl}methyl}}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{{(R)-(4-chlorophenyl){4-[bis(2-methoxyethyl)aminomethyl]phenyl}methyl}}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{{(S)-(4-chlorophenyl){4-[bis(2-methoxyethyl)aminomethyl]phenyl}methyl}}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(RS)-(4-chlorophenyl)[4-[di-n-propylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(R)-(4-chlorophenyl)[4-(di-n-propylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(S)-(4-chlorophenyl)[4-(di-n-propylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(RS)-(4-chlorophenyl)[4-(piperidin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(R)-(4-chlorophenyl)[4-(piperidin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1{(S)-(4-chlorophenyl)[4-(piperidin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(RS)-(4-chlorophenyl)[4-(4-methylpiperazin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(R)-(4-chlorophenyl)[4-(4-methylpiperazin-1-ylmethyl)phenyl]methyl}-3-(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(S)-(4-chlorophenyl)[4-(4-methylpiperazin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(RS)-(4-chlorophenyl)[4-(morpholin-4-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(R)-(4-chlorophenyl)[4-(morpholin-4-ylmethyl)phenyl]methyl}-3-1(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(S)-(4-chlorophenyl)[4-(morpholin-4-ylmethyl)phenyl]methyl}-3-((3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(RS)-(4-chlorophenyl)[4-(diethylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(R)-(4-chlorophenyl)[4-(diethylaminomethyl)phenyl]methyl}-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(S)-(4-chlorophenyl)[4-(diethylaminomethyl)phenyl]methyl}-3[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(RS)-(4-chlorophenyl)[4-(piperazin-2-one-4-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(R)-(4-chlorophenyl)[4-(piperazin-2-one-4-ylmethyl)phenyl]methyl}-3-1(3,5difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(S)-(4-chlorophenyl)[4-(piperazin-2-one-4-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(RS)-(4-chlorophenyl)[4-(imidazol-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(R)-(4-chlorophenyl)[4-(imidazol-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-{(S)-(4-chlorophenyl)[4-(imidazol-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(RS)-1-{(4-chlorophenyl)[4-(N,N-dimethylcarbamoyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(R)-1-{(4-chlorophenyl)[4-(N,N-dimethylcarbamoyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(S)-1-{(4chlorophenyl)[4-(N,N-dimethylcarbamoyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(RS)-1-{(4-chlorophenyl)[4-(N-ethylcarbamoyl)phenyl]methyl)}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(R)-1-{(4-chlorophenyl)[4-(N-ethylcarbamoyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(S)-1-{(4-chlorophenyl)[4-(N-ethylcarbamoyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(RS)-1-[4-carbamoylphenyl)(4-chlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(R)-1-[(4-carbamoylphenyl)(4-chlorophenyl)methyl-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(S)-1-[(4-carbamoylphenyl)(4-chlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-[bis(4-chlorophenyl)methyl]-3-[(3,5-dichlorophenyl)(methylsulfonyl)methylene]azetidine,1-benzhydryl-3-[(3-methylsulfanylphenyl)(methylsulfonyl)methylene]azetidine,1-benzhydryl-3-[(3-methylsulfanylmethyl)phenyl)](methylsulfonyl)methylene]azetidine,1-[bis(4-chlorophenyl)methyl]-3-3-[(3-cyanophenyl)(methylsulfonyl)methylene]azetidine,1-[bis(4-chlorophenyl)methyl]-3-[(3-carbamoylphenyl)(methylsulfonyl)methylene]azetidine,1-[bis(4-chlorophenyl)methyl]-3-[(3-methoxyphenyl)(methylsulfonyl)methylene]azetidine,1-[bis(4-chlorophenyl)methyl]-3-[(3-hydroxyphenyl)(methylsulfonyl)methylene]azetidine,1-[bis(4-chlorophenyl)methyl]-3-[(methylsulfonyl)(3-pyrrolidinylphenyl)methylene]azetidine,1-[bis(4-chlorophenyl)methyl]-3-[(3-hydroxymethylphenyl)(methylsulfonyl)methylene]azetidine,1-[bis(4-chlorophenyl)methyl]-3-((methylsulfonyl)[3-(N-piperidylcarbamoyl)phenyl]methylene}azetidine,1-[bis(4-chlorophenyl)methyl]-3-[(methylsulfonyl)(3-trifluoromethylsulfanylphenyl)(methylsulfonyl)-methylene]azetidine,1-[bis(4-fluorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-[bis(2-fluorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-[bis(3-fluorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(RS)-1-[(4-chlorophenyl)(thiazol-2-yl)methyl]-3-[(methylsulfonyl)(phenyl)methylene]azetidine,(R)-1-[(4-chlorophenyl)(thiazol-2-yl)methyl]-3-[(methylsulfonyl)(phenyl)methylene]azetidine,(S)-1-[(4-chlorophenyl)(thiazol-2-yl)methyl]-3-[(methylsulfonyl)(phenyl)methylene]azetidine,(RS)-1-[(4-chlorophenyl)(thien-2-yl)methyl)-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(R)-1-[(4-chlorophenyl)(thien-2-yl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(S)-1-[(4-chlorophenyl)(thien-2-yl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-benzhydryl-3-[(ethylsulfonyl)(phenyl)methylene]azetidine,1-[bis(4-chlorophenyl)methyl]-3-{{3-[N-(4-methylpiperazinyl)carbamoyl]phenyl}(methylsulfonyl)methylene)azetidine,1-[bis(4-chlorophenyl)methyl]-3-{[3-(2,2-dimethylcarbohydrazido)phenyl](methylsulfonyl)methylene}azetidine,1-[bis(thien-2-yl)methyl]-3[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-[bis(p-tolyl)methyl]-3-[(methylsulfonyl)(phenyl)methylene]azetidine,1-[(4-chlorophenyl)(4-hydroxymethylphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-[bis(4-chlorophenyl)methyl]-3-[(3-methylaminophenyl)(methylsulfonyl)methylene]azetidine,(RS)-1-[(4-chlorophenyl)(thiazol-2-yl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(R)-1-[(4-chlorophenyl)(thiazol-2-yl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,(S)-1-[(4-chlorophenyl)(thiazol-2-yl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,1-[bis(4-chlorophenyl)methyl]-3-[(methylsulfonyl)(2-methoxycarbonylthien-5-yl)methylene]azetidine,(RS)-1-[bis(4-chlorophenyl)methyl]3-hydroxy-3-[(methylsulfonyl)(2-methoxycarbonylthien-5-yl)methyl]azetidine,1-[bis(4-chlorophenyl)methyl]-3-[(2-isobutylaminocarbonylthien-5-yl)(methylsulfonyl)methylene]azetidine,1-[bis(4-chlorophenyl)methyl]-3-[(RS)-(3-methoxycarbonylphenyl)(methylsulfonyl)methyl]azetidin-3-ol,1-[bis(4-chlorophenyl)methyl]-3-[(RS)-(methylsulfonyl)(pyridin-4-yl)methyl]azetidin-3-ol,1-[bis(4-chlorophenyl)methyl]-3-((RS)-(methylsulfonyl)(pyridin-3-yl)methyl]azetidin-3-ol,3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(3-(morpholin-4-yl)propyl)benzamide,3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(3-dimethylaminopropyl)benzamide,3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-(pyrrolidin-1-yl)ethyl)benzamide,3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-dimethylamino-1-methylethyl)benzamide,3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(piperidin-1-yl)benzamide,3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-isobutylbenzamide,3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(3-(imidazol-1-yl)propyl)benzamide,3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-dimethylaminoethyl)benzamide,N′-methylhydrazide of3-({1-[bis(4-chlorophenyl)methyl-3-azetidin-3-ylidene}(methanesulfonyl)methyl)benzoicacid,3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-(morpholin-4-yl)ethyl)benzamide,3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(1-ethylpyrrolidin-2-ylmethyl)benzamide,3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2,2-dimethylpropyl)benzamide,3-({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(cyclohexylmethyl)benzamide,3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(cyclopropylmethyl)benzamide,3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-methylbutyl)benzamide,3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-phenylpropyl)benzamide,3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(tetrahydrofuran-2-ylmethyl)benzamide,3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2,2-diphenylethyl)benzamide,3-({1-[bis(4-chlorophenylbmethyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-ethylbutyl)benzamide,methyl ester of4-{[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)benzoylamino]methyl}cyclohexanecarboxylicacid,2-amino-1-{4-[3-({1-[bis(4-chlorophenyl)methyl]-azetidin-3ylidene}(methanesulfonyl)methyl)phenyl]-piperazin-1-yl}ethanone,tert-butyl ester of(2-{4-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazin-1-yl}-2-oxoethyl)carbamicacid,1-(4-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methylphenyl]piperazin-1-yl]-2-(methylamino)ethanone,tert-butyl ester of(2-{4-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazin-1-yl}-2-oxoethyl)-N-methylcarbamicacid, N-methylamide of4-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazine-1-carbothioicacid, N-methylamide of4-[3-({1-[bis(4-chlorophenyl)methyl]-azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazine-1-carboxylicacid, methyl ester of4-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazine-1-carboxylicacid,1-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]-4-isobutylpiperazine,1-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]-4-ethylpiperazine,4-acetyl-1-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazine,1-{4-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazin-1-yl}-2-dimethylaminoethanone,1-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazine,tert-butyl ester of4-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazine-1-carboxylicacid,1-[bis(4-methoxycarbonylphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,3-acetoxy-1-[bis(4-methoxycarbonylphenyl)methyl]-3-[(RS)-(3,5-difluorophenyl)(methylsulfonyl)methyl]-azetidine,(RS)-4-[4-((4-chlorophenyl){3-[(3,5difluorophenyl)(methanesulfonyl)methylene]azetidin-1-yl}methyl)benzyl]morpholine,4-(4-{3-[(1-benzhydrylazetidin-3-ylidene)(methanesulfonyl)methyl]phenoxy}butyl)morpholine,4-(4-{3-[(1-benzhydrylazetidin-3-ylidene)(methanesulfonyl)methyl]phenoxy}propyl)morpholine,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}thien-2-ylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-4-methoxyphenylsulfonamide,N-[4-(N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-sulfamoyl)phenyl]acetamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-4-methylphenylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3,4-dimethoxyphenylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3-fluorophenylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3,4-dichlorophenylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3-cyanophenylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-2,5-dimethoxyphenylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3-trifluoromethylphenylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}naphth-2-ylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}naphth-1-ylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3,4-difluorophenylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-1-methyl-1H-imidazol-4-ylsulfonamide,N-[4-(N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}sulfamoyl)-2-chlorophenyl]acetamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}pyrid-3-ylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-4-fluorophenylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}quinol-8-ylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}phenylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}(phenylmethyl)sulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3,5-difluorophenylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}pyrid-2-ylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-(3-fluoro-5-pyrrolidin-1-ylphenyl)sulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-methyl-4-fluorophenylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-methylquinol-8-ylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-methylphenylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-methyl(phenylmethyl)sulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3-sulfamoylphenylsulfonamide,2-benzenesulfonyl-N-{1-[bis(4-chlorophenyl)methyl]-azetidin-3-yl}acetamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-2-(4-toluene-4-sulfonyl)acetamide,(3-chloro-4-(methylsulfonyl)thiophene-2-carboxy)-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl]amide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3-(2-phenylethylenesulfonyl)propionamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-4-(methylsulfonyl)benzamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-4-(methanesulfonyl)benzamide,(5-(methylsulfonyl)thiophene-2-carboxy)-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}amide,(5-methylsulfonyl-3-methyl-4-vinylthiophene-2-carboxy){-[bis(4-chlorophenyl)methyl]azetidin-3-yl}amide,(RS)-N-{1-[(4-chlorophenyl)(pyridin-3-yl)methyl]-azetidin-3-yl}-3,5-difluorobenzenesulfonamide,(RS)-N-{1-[(4-chlorophenyl)(pyrimidin-5-yl)methyl]azetidin-3-yl}-3,5-difluorobenzenesulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N(6-chloropyrid-2-yl)methylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(6-ethylpyrid-2-yl)methylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(quinol-6-yl)methylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(quinol-5-yl)methylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(isoquinol-5-yl)methylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(pyrid-3-yl)methylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(pyrid-1-oxide-3-yl)methylsulfonamide,N-(1R,2S,4S)-(bicyclo[2.2.1]hept-2-yl)-N-{1-[bis-(4-chlorophenyl)methyl]azetidin-3-yl}methylsulfonamide,N-(1R,2R,4S)-(bicyclo[2.2.1]hept-2-yl)-N-{1-[bis-(4-chlorophenyl)methyl]azetidin-3-yl}methylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(thiazol-2-yl)methylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3-methoxyphenyl)methylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3-(hydroxymethyl)phenyl)methylsulfonamide,ethylN-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(methylsulfonyl)-3-aminobenzoate,N-1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(isobutylpiperid-4-yl)methylsulfonamide,N-benzyl-N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}amine,N-1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3,5-difluorobenzyl)amine,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3,5-difluorobenzyl)methylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(pyrid-3-ylmethyl)methylsulfonamide,N-{1-[bis(4-fluorophenyl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,(RS)-N-{1-[(4-chlorophenyl)(pyrid-3-yl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,(R)-N-1-[(4chlorophenyl)(pyrid-3-yl)methyl]azetidin-3-yl)-N-(3,5-difluorophenyl)methylsulfonamide,(S)-N-{1-[(4-chlorophenyl)(pyrid-5-yl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,(RS)-N-{1-[(4-chlorophenyl)(pyrid-4-yl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,(R)-N-{1-[(4-chlorophenyl)(pyrid4-yl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,(S)-N-{1-[(4-chlorophenyl)(pyrid-4-yl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,(RS)-N-1-[(4-chlorophenyl)(pyrimidin-5-yl)methyl]azetidin-yl)-N-(3,5-difluorophenyl)methylsulfonamide,(R)-N-{1-[(4-chlorophenyl)(pyrimidin-5-yl)methyl]-azetidin-3-yl)-N-(3,5-difluorophenyl)methylsulfonamide,(S)-N-1-[(4-chlorophenyl)(pyrimidin-5-yl)methyl]-azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)benzylsulfonamide,their optical isomers and their pharmaceutically acceptable salts. 9.The pharmaceutical composition as. claimed in claim 7, for which thecompound of formula (I) is chosen from the following compounds:1-[bis(4-chlorophenyl)methyl]3-3-[(RS)-(3,5-difluorophenyl)(methylsulfonyl)methyl]azetidin-3-ol,3-acetoxy-1-[bis(4-chlorophenyl)methyl]-3-[(RS)-(3,5-difluorophenyl)(methylulphonyl)methyl)methylsulfonylmethyl]azetidine,1-[bis(4-chlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,their optical isomers and their pharmaceutically acceptable salts. 10.The pharmaceutical composition as claimed in claim 6, in which the CB1[lacuna] antagonist is SR141716, its hydrates and its pharmaceuticallyacceptable salts or LY320135 and its pharmaceutically acceptable salts.11. The pharmaceutical composition as claimed in one of claims 6 to 10for a use which is simultaneous, separate or spread out over time. 12.The pharmaceutical composition as claimed in one of claim 6 to 11,comprising 0.5 to mg of sibutramine and 0.1 to 200 mg of the CB1[lacuna] antagonist.